1

1.0 Introduction
Minerals has always been a part of a human’s life through food intake or exposure without us even realizing it. Zinc is a very good example of a mineral that is crucial to living organisms mainly humans and animals. Most rocks and other minerals consists of zinc in varying amounts and it enters the air, water and soil due to natural processes or activities done by humans.

Zinc is a bluish-silver element that is widely used in industries to make cosmetics, ointments, lotions, weapons used in the army and many more. It is also popular in manufacturing roofing materials or into chemical compounds such as zinc oxide. This white powder is used in everything from sunscreen to solar cells to nuclear reactors where its used to prevent corrosion. (Pappas.S,2015)
It is known that a range of 2-4 grams of zinc are present throughout the human body (Wapnir R.,1990,ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “The use of zinc in metal alloys and medicinal lotions dates back before the time of Christ. Currently, most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. Some studies support the use of zinc gluconate lozenges to treat the common cold, but there are insufficient data at this time to recommend the routine use of these lozenges. Zinc is an essential co-factor in a variety of cellular processes including DNA synthesis, behavioral responses, reproduction, bone formation, growth, and wound heal- ing. Zinc is a relatively common metal with an average concentration of 50 mg/ kg soil and a range of 10u2013300 mg/kg soil. Meat, seafood, dairy products, nuts, legumes, and whole grains contain relatively high concentrations of zinc. The mobility of zinc in anaerobic environments is poor and therefore severe zinc contamination occurs primarily near points sources of zinc release. The recom- mended daily allowance for adults is 15 mg zinc. The ingestion of 1u20132 g zinc sulfate produces emesis. Zinc compounds can produce irritation and corrosion of the gastrointestinal tract, along with acute renal tubular necrosis and inter- stitial nephritis. Inhalation of high concentrations of zinc chloride from smoke bombs detonated in closed spaces may cause chemical pneumonitis and adult respiratory distress syndrome. In the occupational setting inhalation of fumes from zinc oxide is the most common cause of metal fume fever (fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, salivation). Zinc compounds are not suspected carcinogens. Treatment of zinc toxicity is supportive. Calcium disodium ethylenediaminetetraacetate (CaNa2 EDTA) is the chelator of choice based on case reports that demonstrate normalization of zinc concentrations, but there are few clinical data to confirm the efficacy of this agent.”, “author” : { “dropping-particle” : “”, “family” : “Barceloux”, “given” : “Donald G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Toxicology”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “1999” }, “page” : “231-237”, “title” : “Zinc”, “type” : “article-journal”, “volume” : “37” }, “uris” : “http://www.mendeley.com/documents/?uuid=2537c6e5-eb9d-4eeb-a515-edf1b4e5c0c0” } , “mendeley” : { “formattedCitation” : “(Barceloux, 1999)”, “manualFormatting” : “Barceloux, 1999)”, “plainTextFormattedCitation” : “(Barceloux, 1999)”, “previouslyFormattedCitation” : “(Barceloux, 1999)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Barceloux, 1999). Although this trace element is mostly present in the brain, muscle, bones, kidney and liver, the highest concentration of zinc is found in the prostate and parts of the eye ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.4172/2161-0495.S3-001”, “ISSN” : “21610495”, “abstract” : “The human body has an elaborate system for managing and regulating the amount of key trace metals circulating in blood and stored in cells. Nutrient metals from our diet are incorporated into blood if blood levels are depleted, transported into cells if cellular levels are inadequate, or excreted if blood and cell levels are sufficient or overloaded. When this system fails to function properly, abnormal levels and ratios of trace metals can develop. One of the most common trace-metal imbalances is elevated copper and depressed zinc. The ratio of copper to zinc is clinically more important than the concentration of either of these trace metals 1.”, “author” : { “dropping-particle” : “”, “family” : “Osredkar”, “given” : “Josko”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Toxicology”, “id” : “ITEM-1”, “issue” : “01”, “issued” : { “date-parts” : “2011” }, “title” : “Copper and Zinc, Biological Role and Significance of Copper/Zinc Imbalance”, “type” : “article-journal”, “volume” : “s3” }, “uris” : “http://www.mendeley.com/documents/?uuid=c6c5c2a6-a018-4b9a-92ee-cae9eb3343da” } , “mendeley” : { “formattedCitation” : “(Osredkar, 2011)”, “manualFormatting” : “(Osredkar, 2011”, “plainTextFormattedCitation” : “(Osredkar, 2011)”, “previouslyFormattedCitation” : “(Osredkar, 2011)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Osredkar, 2011). Zinc is the second most abundant trace element that is found in the human body apart from iron (Vasak ; Hasler,2000; ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Stefanidou, Maravelias, Dona, & Spiliopoulou, 2006)”, “manualFormatting” : “Stefanidou, Maravelias, Dona, & Spiliopoulou, 2006)”, “plainTextFormattedCitation” : “(Stefanidou, Maravelias, Dona, & Spiliopoulou, 2006)”, “previouslyFormattedCitation” : “(Stefanidou, Maravelias, Dona, & Spiliopoulou, 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Stefanidou, Maravelias, Dona, ; Spiliopoulou, 2006). Zinc is involved in most cell processes including DNA synthesis, normal growth, brain development, behavioural response, reproduction, foetal development, membrane stability, bone formation and wound healing. There are many benefits of zinc in the human biological system such as to fight certain diseases but many are still in the dark about the importance or effects one mineral can bring to oneself.

Good food sources of zinc include seafood, beef, lamb, eggs, whole grains, nuts and yoghurt. Based on the list of food sources, we can conclude that the type of diet we follow affects the concentration of zinc that is present in our body whether it is sufficient or the other way around. Being zinc deficient can influence brain activity, immune system, male reproductive system, pregnancy and the speed of wound healing. Excess of zinc on the other hand can cause some temporary effects but some cases are more serious than others that can lead up to permanent damages.
This review describes the function of zinc, effects of high concentration of the mineral, with focus on the significance of zinc in the human body in terms of immune system, brain, skin, male reproductive system, pregnancy and pre-menstrual syndrome.
2.0 FUNCTION OF ZINC IN HUMAN BODY
There are 3 crucial roles involving zinc in human body such as catalytical, structural and regulatory. Zinc plays a role as catalyst to 300 different kinds of enzymes during their chemical reaction. Zinc is needed in catalysis and co-catalysis by the enzymes which undergo many cell processes including DNA synthesis, normal growth, brain development, behavioural response, reproduction, foetal development, membrane stability, bone formation and wound healing ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “The use of zinc in metal alloys and medicinal lotions dates back before the time of Christ. Currently, most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. Some studies support the use of zinc gluconate lozenges to treat the common cold, but there are insufficient data at this time to recommend the routine use of these lozenges. Zinc is an essential co-factor in a variety of cellular processes including DNA synthesis, behavioral responses, reproduction, bone formation, growth, and wound heal- ing. Zinc is a relatively common metal with an average concentration of 50 mg/ kg soil and a range of 10u2013300 mg/kg soil. Meat, seafood, dairy products, nuts, legumes, and whole grains contain relatively high concentrations of zinc. The mobility of zinc in anaerobic environments is poor and therefore severe zinc contamination occurs primarily near points sources of zinc release. The recom- mended daily allowance for adults is 15 mg zinc. The ingestion of 1u20132 g zinc sulfate produces emesis. Zinc compounds can produce irritation and corrosion of the gastrointestinal tract, along with acute renal tubular necrosis and inter- stitial nephritis. Inhalation of high concentrations of zinc chloride from smoke bombs detonated in closed spaces may cause chemical pneumonitis and adult respiratory distress syndrome. In the occupational setting inhalation of fumes from zinc oxide is the most common cause of metal fume fever (fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, salivation). Zinc compounds are not suspected carcinogens. Treatment of zinc toxicity is supportive. Calcium disodium ethylenediaminetetraacetate (CaNa2 EDTA) is the chelator of choice based on case reports that demonstrate normalization of zinc concentrations, but there are few clinical data to confirm the efficacy of this agent.”, “author” : { “dropping-particle” : “”, “family” : “Barceloux”, “given” : “Donald G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Toxicology”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “1999” }, “page” : “231-237”, “title” : “Zinc”, “type” : “article-journal”, “volume” : “37” }, “uris” : “http://www.mendeley.com/documents/?uuid=2537c6e5-eb9d-4eeb-a515-edf1b4e5c0c0” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1016/S0165-6147(00)01476-0”, “ISSN” : “01656147”, “PMID” : “10838605”, “abstract” : “Infections can cause mortality when the immune system is damaged. The catalytic, structural (in zinc-finger proteins) and regulatory roles of zinc mean that this ion is involved in the maintenance of an effective immune response. Both zinc deficiency and impaired cell-mediated immunity combine during aging to result in increased susceptibility to infection. Dietary supplementation with the recommended daily allowance of zinc for between one and two months decreases the incidence of infection and increases the survival rate following infection in the elderly. This article reviews the biochemical pathways through which zinc might act to increase immunoresistance to infection in the elderly. Copyright (C) 2000 Elsevier Science Ltd.”, “author” : { “dropping-particle” : “”, “family” : “Mocchegiani”, “given” : “Eugenio”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Muzzioli”, “given” : “Mario”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Giacconi”, “given” : “Robertina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Trends in Pharmacological Sciences”, “id” : “ITEM-2”, “issue” : “6”, “issued” : { “date-parts” : “2000” }, “page” : “205-208”, “title” : “Zinc and immunoresistance to infection in aging: New biological tools”, “type” : “article-journal”, “volume” : “21” }, “uris” : “http://www.mendeley.com/documents/?uuid=16269cc8-189b-4a60-b463-4986730ba4ce” }, { “id” : “ITEM-3”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-3”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Barceloux, 1999; Mocchegiani, Muzzioli, & Giacconi, 2000; Stefanidou et al., 2006)”, “plainTextFormattedCitation” : “(Barceloux, 1999; Mocchegiani, Muzzioli, & Giacconi, 2000; Stefanidou et al., 2006)”, “previouslyFormattedCitation” : “(Barceloux, 1999; Mocchegiani, Muzzioli, & Giacconi, 2000; Stefanidou et al., 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Barceloux, 1999; Mocchegiani, Muzzioli, ; Giacconi, 2000; Stefanidou et al., 2006). When zinc is absent in their structure, it leads to an increase of oxidation and damages the immune cell membrane and protein. This means that zinc is needed in structure of protein and cell membrane. Zinc binds with metalloprotein,MTs and plays an important role in the structural and functional of other proteins especially in DNA replication and reverse transcription ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0165-6147(00)01476-0”, “ISSN” : “01656147”, “PMID” : “10838605”, “abstract” : “Infections can cause mortality when the immune system is damaged. The catalytic, structural (in zinc-finger proteins) and regulatory roles of zinc mean that this ion is involved in the maintenance of an effective immune response. Both zinc deficiency and impaired cell-mediated immunity combine during aging to result in increased susceptibility to infection. Dietary supplementation with the recommended daily allowance of zinc for between one and two months decreases the incidence of infection and increases the survival rate following infection in the elderly. This article reviews the biochemical pathways through which zinc might act to increase immunoresistance to infection in the elderly. Copyright (C) 2000 Elsevier Science Ltd.”, “author” : { “dropping-particle” : “”, “family” : “Mocchegiani”, “given” : “Eugenio”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Muzzioli”, “given” : “Mario”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Giacconi”, “given” : “Robertina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Trends in Pharmacological Sciences”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : “2000” }, “page” : “205-208”, “title” : “Zinc and immunoresistance to infection in aging: New biological tools”, “type” : “article-journal”, “volume” : “21” }, “uris” : “http://www.mendeley.com/documents/?uuid=16269cc8-189b-4a60-b463-4986730ba4ce” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1016/S0753-3322(03)00081-7”, “ISBN” : “0753-3322”, “ISSN” : “07533322”, “PMID” : “14652165”, “abstract” : “Zinc is one of the most abundant nutritionally essential elements in the human body. It is found in all body tissues with 85% of the whole body zinc in muscle and bone, 11% in the skin and the liver and the remaining in all the other tissues. In multicellular organisms, virtually all zinc is intracellular, 30-40% is located in the nucleus, 50% in the cytoplasm, organelles and specialized vesicles (for digestive enzymes or hormone storage) and the remainder in the cell membrane. Zinc intake ranges from 107 to 231 u03bcmol/d depending on the source, and human zinc requirement is estimated at 15 mg/d. Zinc has been shown to be essential to the structure and function of a large number of macromolecules and for over 300 enzymic reactions. It has both catalytic and structural roles in enzymes, while in zinc finger motifs, it provides a scaffold that organizes protein sub-domains for the interaction with either DNA or other proteins. It is critical for the function of a number of metalloproteins, inducing members of oxido-reductase, hydrolase ligase, lyase family and has co-activating functions with copper in superoxide dismutase or phospholipase C. The zinc ion (Zn++) does not participate in redox reactions, which makes it a stable ion in a biological medium whose potential is in constant flux. Zinc ions are hydrophilic and do not cross cell membranes by passive diffusion. In general, transport has been described as having both saturable and non-saturable components, depending on the Zn(II) concentrations involved. Zinc ions exist primarily in the form of complexes with proteins and nucleic acids and participate in all aspects of intermediary metabolism, transmission and regulation of the expression of genetic information, storage, synthesis and action of peptide hormones and structural maintenance of chromatin and biomembranes. u00a9 2003 Published by u00c9ditions scientifiques et mu00e9dicales Elsevier SAS.”, “author” : { “dropping-particle” : “”, “family” : “Tapiero”, “given” : “Haim”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tew”, “given” : “Kenneth D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Biomedicine and Pharmacotherapy”, “id” : “ITEM-2”, “issue” : “9”, “issued” : { “date-parts” : “2003” }, “page” : “399-411”, “title” : “Trace elements in human physiology and pathology: Zinc and metallothioneins”, “type” : “article-journal”, “volume” : “57” }, “uris” : “http://www.mendeley.com/documents/?uuid=a11de984-e447-4e07-a647-75da70590a1f” }, { “id” : “ITEM-3”, “itemData” : { “DOI” : “10.1007/s00204-011-0775-1”, “ISBN” : “0340-5761”, “ISSN” : “03405761”, “PMID” : “22071549”, “abstract” : “The importance of micronutrients in health and nutrition is undisputable, and among them, zinc is an essential element whose significance to health is increasingly appreciated and whose deficiency may play an important role in the appearance of diseases. Zinc is one of the most important trace elements in the organism, with three major biological roles, as catalyst, structural, and regulatory ion. Zinc-binding motifs are found in many proteins encoded by the human genome physiologically, and free zinc is mainly regulated at the single-cell level. Zinc has critical effect in homeostasis, in immune function, in oxidative stress, in apoptosis, and in aging, and significant disorders of great public health interest are associated with zinc deficiency. In many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, autoimmune diseases, aging, age-related degenerative diseases, and Wilson’s disease, the concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress, and lead to the generation of inflammatory cytokines. In these diseases, oxidative stress and chronic inflammation may play important causative roles. It is therefore important that status of zinc is assessed in any case and zinc deficiency is corrected, since the unique properties of zinc may have significant therapeutic benefits in these diseases. In the present paper, we review the zinc as a multipurpose trace element, its biological role in homeostasis, proliferation and apoptosis and its role in immunity and in chronic diseases, such as cancer, diabetes, depression, Wilson’s disease, Alzheimer’s disease, and other age-related diseases.”, “author” : { “dropping-particle” : “”, “family” : “Chasapis”, “given” : “Christos T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “Chara A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Loutsidou”, “given” : “Ariadni C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “Maria E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-3”, “issue” : “4”, “issued” : { “date-parts” : “2012” }, “page” : “521-534”, “title” : “Zinc and human health: An update”, “type” : “article-journal”, “volume” : “86” }, “uris” : “http://www.mendeley.com/documents/?uuid=22ad5135-300c-48b7-be91-bb74c6896aa9” } , “mendeley” : { “formattedCitation” : “(Chasapis, Spiliopoulou, Loutsidou, & Stefanidou, 2012; Mocchegiani et al., 2000; Tapiero & Tew, 2003)”, “plainTextFormattedCitation” : “(Chasapis, Spiliopoulou, Loutsidou, & Stefanidou, 2012; Mocchegiani et al., 2000; Tapiero & Tew, 2003)”, “previouslyFormattedCitation” : “(Chasapis, Spiliopoulou, Loutsidou, & Stefanidou, 2012; Mocchegiani et al., 2000; Tapiero & Tew, 2003)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Chasapis, Spiliopoulou, Loutsidou, ; Stefanidou, 2012; Mocchegiani et al., 2000; Tapiero ; Tew, 2003). Zinc ions are hydrophilic and cannot pass through cell membranes through passive diffusion. Transportation of zinc related to saturation and unsaturation of components depending on the amount of zinc. Gene sequence is regulated by zinc finger protein which acts as transcription factors. In addition, zinc also encourages the release of hormones and nerve impulse transmissions ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “See, stats, and : https : / / www . researchgate . net / publication / 277014212 A human Article CITATIONS 4 READS 1 , 028 3 , including : Some : organ Debjit HIPER 165 SEE Chiranjib Srikrupa 28 SEE All . The . All – text and , letting . Zinc is an essential nutrient for human health . Ensuring adequate levels of zinc intake should be a key component in efforts to reduce child illness , enhance physical growth and decrease mortality in developing countries . In spite of the proven benefits of adequate zinc nutrition , approximately 2 billion people still remain risk of zinc deficiency . Zinc is found in over 200 enzymes and hormones in mankind . It is a natural element found in all plants and animals , and is widely available in over – the – counter vitamin supplements . Zinc is essential to life . It is a natural element found in all plants and animals and plays a crucial part in the health of our skin , teeth , bones , hair , nails , muscles , nerves and brain function Zinc is essential for growth . It is used to control the enzymes that operate and renew the cells in our bodies . The formation of DNA , the basis of all life on our planet , would not be possible without zinc . Zinc deficiency was a major etiological factor in the syndrome of adolescent nutritional dwarfism , that had been identified mid – eastern countries . Zinc deficiency is an important public health problem , Nutritionists have been concerned that zinc deficiency affects large numbers of women and children in India and worldwide . In recent survey by WHO , zinc deficiency found most of the Indian population and Zinc supplement is used to commonly to enhance wound healing and treatment of pneumonia . Zinc gluconate lozenges , taken at the first sign of a common cold , reduce duration and symptom severity by 42% according to a 1992 study . Trace element zinc is important in maintaining the healthy growth of the human body , especially for infants and young children ‘ s growth and development .”, “author” : { “dropping-particle” : “”, “family” : “Bhowmik”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chiranjib”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Int. J. Pharm. Biomed. Sci.”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2010” }, “page” : “5-11”, “title” : “A potential medicinal importance of zinc in human health and chronic disease”, “type” : “article-journal”, “volume” : “1” }, “uris” : “http://www.mendeley.com/documents/?uuid=81621b14-ff97-4e2c-8fa3-2ae716da8b22” } , “mendeley” : { “formattedCitation” : “(Bhowmik & Chiranjib, 2010)”, “plainTextFormattedCitation” : “(Bhowmik & Chiranjib, 2010)”, “previouslyFormattedCitation” : “(Bhowmik & Chiranjib, 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Bhowmik ; Chiranjib, 2010). Enzymatic activities are enhanced by zinc and also stabilizes the protein whereby the mineral acts act as an activator or inhibitor ion ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0165-6147(00)01476-0”, “ISSN” : “01656147”, “PMID” : “10838605”, “abstract” : “Infections can cause mortality when the immune system is damaged. The catalytic, structural (in zinc-finger proteins) and regulatory roles of zinc mean that this ion is involved in the maintenance of an effective immune response. Both zinc deficiency and impaired cell-mediated immunity combine during aging to result in increased susceptibility to infection. Dietary supplementation with the recommended daily allowance of zinc for between one and two months decreases the incidence of infection and increases the survival rate following infection in the elderly. This article reviews the biochemical pathways through which zinc might act to increase immunoresistance to infection in the elderly. Copyright (C) 2000 Elsevier Science Ltd.”, “author” : { “dropping-particle” : “”, “family” : “Mocchegiani”, “given” : “Eugenio”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Muzzioli”, “given” : “Mario”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Giacconi”, “given” : “Robertina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Trends in Pharmacological Sciences”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : “2000” }, “page” : “205-208”, “title” : “Zinc and immunoresistance to infection in aging: New biological tools”, “type” : “article-journal”, “volume” : “21” }, “uris” : “http://www.mendeley.com/documents/?uuid=16269cc8-189b-4a60-b463-4986730ba4ce” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1007/s00204-011-0775-1”, “ISBN” : “0340-5761”, “ISSN” : “03405761”, “PMID” : “22071549”, “abstract” : “The importance of micronutrients in health and nutrition is undisputable, and among them, zinc is an essential element whose significance to health is increasingly appreciated and whose deficiency may play an important role in the appearance of diseases. Zinc is one of the most important trace elements in the organism, with three major biological roles, as catalyst, structural, and regulatory ion. Zinc-binding motifs are found in many proteins encoded by the human genome physiologically, and free zinc is mainly regulated at the single-cell level. Zinc has critical effect in homeostasis, in immune function, in oxidative stress, in apoptosis, and in aging, and significant disorders of great public health interest are associated with zinc deficiency. In many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, autoimmune diseases, aging, age-related degenerative diseases, and Wilson’s disease, the concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress, and lead to the generation of inflammatory cytokines. In these diseases, oxidative stress and chronic inflammation may play important causative roles. It is therefore important that status of zinc is assessed in any case and zinc deficiency is corrected, since the unique properties of zinc may have significant therapeutic benefits in these diseases. In the present paper, we review the zinc as a multipurpose trace element, its biological role in homeostasis, proliferation and apoptosis and its role in immunity and in chronic diseases, such as cancer, diabetes, depression, Wilson’s disease, Alzheimer’s disease, and other age-related diseases.”, “author” : { “dropping-particle” : “”, “family” : “Chasapis”, “given” : “Christos T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “Chara A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Loutsidou”, “given” : “Ariadni C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “Maria E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-2”, “issue” : “4”, “issued” : { “date-parts” : “2012” }, “page” : “521-534”, “title” : “Zinc and human health: An update”, “type” : “article-journal”, “volume” : “86” }, “uris” : “http://www.mendeley.com/documents/?uuid=22ad5135-300c-48b7-be91-bb74c6896aa9” } , “mendeley” : { “formattedCitation” : “(Chasapis et al., 2012; Mocchegiani et al., 2000)”, “plainTextFormattedCitation” : “(Chasapis et al., 2012; Mocchegiani et al., 2000)”, “previouslyFormattedCitation” : “(Chasapis et al., 2012; Mocchegiani et al., 2000)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Chasapis et al., 2012; Mocchegiani et al., 2000). Furthermore, zinc is also abundant in the forebrain which acts as a modulator of synaptic neuron-transmission and modulator to cellular signal transduction processes ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1002/mawe.200290008”, “ISSN” : “09335137”, “abstract” : “Abstract Zinc is an element that is essential for cell proliferation and differentiation. Zinc is a structural constituent of a great number of proteins including metabolic enzymes, cellular signaling proteins and transcription factors. The total intracellular concentration of zinc … \n”, “author” : { “dropping-particle” : “”, “family” : “Beyersmann”, “given” : “Detmar”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Materialwissenschaft und Werkstofftechnik”, “id” : “ITEM-1”, “issue” : “12”, “issued” : { “date-parts” : “2002” }, “page” : “764-769”, “title” : “Homeostasis and cellular functions of zinc”, “type” : “article-journal”, “volume” : “33” }, “uris” : “http://www.mendeley.com/documents/?uuid=171682b0-e403-4e88-adf9-a6c313bbae0d” } , “mendeley” : { “formattedCitation” : “(Beyersmann, 2002)”, “manualFormatting” : “(Beyersmann, 2002”, “plainTextFormattedCitation” : “(Beyersmann, 2002)”, “previouslyFormattedCitation” : “(Beyersmann, 2002)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Beyersmann, 2002;ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Stefanidou et al., 2006)”, “manualFormatting” : “Stefanidou et al., 2006)”, “plainTextFormattedCitation” : “(Stefanidou et al., 2006)”, “previouslyFormattedCitation” : “(Stefanidou et al., 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Stefanidou et al., 2006). Zinc homeostasis is important to regulate its absorption, distribution, cellular uptake and excretion. (Vallee;Falchuk,993). Cytosol is where zinc is abundant followed by nucleus and other part that is associated with membranes (Vallee;Falchuk,1993;ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.3390/ijerph7041342”, “ISBN” : “1660-4601”, “ISSN” : “16604601”, “PMID” : “20617034”, “abstract” : “Compared to several other metal ions with similar chemical properties, zinc is relatively harmless. Only exposure to high doses has toxic effects, making acute zinc intoxication a rare event. In addition to acute intoxication, long-term, high-dose zinc supplementation interferes with the uptake of copper. Hence, many of its toxic effects are in fact due to copper deficiency. While systemic homeostasis and efficient regulatory mechanisms on the cellular level generally prevent the uptake of cytotoxic doses of exogenous zinc, endogenous zinc plays a significant role in cytotoxic events in single cells. Here, zinc influences apoptosis by acting on several molecular regulators of programmed cell death, including caspases and proteins from the Bcl and Bax families. One organ where zinc is prominently involved in cell death is the brain, and cytotoxicity in consequence of ischemia or trauma involves the accumulation of free zinc. Rather than being a toxic metal ion, zinc is an essential trace element. Whereas intoxication by excessive exposure is rare, zinc deficiency is widespread and has a detrimental impact on growth, neuronal development, and immunity, and in severe cases its consequences are lethal. Zinc deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication.”, “author” : { “dropping-particle” : “”, “family” : “Plum”, “given” : “Laura M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rink”, “given” : “Lothar”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hajo”, “given” : “Haase”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Environmental Research and Public Health”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2010” }, “page” : “1342-1365”, “title” : “The essential toxin: Impact of zinc on human health”, “type” : “article-journal”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=f4d7d615-4621-40fd-95d3-73703581063e” } , “mendeley” : { “formattedCitation” : “(Plum, Rink, & Hajo, 2010)”, “manualFormatting” : “Plum, Rink, & Hajo, 2010)”, “plainTextFormattedCitation” : “(Plum, Rink, & Hajo, 2010)”, “previouslyFormattedCitation” : “(Plum, Rink, & Hajo, 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Plum, Rink, ; Hajo, 2010). The function of zinc homeostasis is used to prevent the accumulation of zinc in excess. There are two protein families involve in zinc transportation which are zinc importer. (zip;zrt-,Irt –like proteins) family and zinc transporter ( znT) family. Zinc importer with 14 proteins is used to transport zinc into cytosol and zinc transporter with 10 proteins transports zinc out of cytosol ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1146/annurev-nutr-033009-083312”, “ISBN” : “0199-9885\n1545-4312”, “ISSN” : “0199-9885”, “PMID” : “19400752”, “abstract” : “Research advances defining how zinc is transported into and out of cells and organelles have increased exponentially within the past five years. Research has progressed through application of molecular techniques including genomic analysis, cell transfection, RNA interference, kinetic analysis of ion transport, and application of cell and animal models including knockout mice. The knowledge base has increased for most of 10 members of the ZnT family and 14 members of the Zrt-, Irt-like protein (ZIP) family. Relative to the handling of dietary zinc is the involvement of ZnT1, ZIP4, and ZIP5 in intestinal zinc transport, involvement of ZIP10 and ZnT1 in renal zinc reabsorption, and the roles of ZIP5, ZnT2, and ZnT1 in pancreatic release of endogenous zinc. These events are major factors in regulation of zinc homeostasis. Other salient findings are the involvement of ZnT2 in lactation, ZIP14 in the hypozincemia of inflammation, ZIP6, ZIP7, and ZIP10 in metastatic breast cancer, and ZnT8 in insulin processing and as an autoantigen in diabetes.”, “author” : { “dropping-particle” : “”, “family” : “Lichten”, “given” : “Louis A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cousins”, “given” : “Robert J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Annual Review of Nutrition”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2009” }, “page” : “153-176”, “title” : “Mammalian Zinc Transporters: Nutritional and Physiologic Regulation”, “type” : “article-journal”, “volume” : “29” }, “uris” : “http://www.mendeley.com/documents/?uuid=c34aaf39-d4df-499f-a83a-0d4d11415479” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.3390/ijerph7041342”, “ISBN” : “1660-4601”, “ISSN” : “16604601”, “PMID” : “20617034”, “abstract” : “Compared to several other metal ions with similar chemical properties, zinc is relatively harmless. Only exposure to high doses has toxic effects, making acute zinc intoxication a rare event. In addition to acute intoxication, long-term, high-dose zinc supplementation interferes with the uptake of copper. Hence, many of its toxic effects are in fact due to copper deficiency. While systemic homeostasis and efficient regulatory mechanisms on the cellular level generally prevent the uptake of cytotoxic doses of exogenous zinc, endogenous zinc plays a significant role in cytotoxic events in single cells. Here, zinc influences apoptosis by acting on several molecular regulators of programmed cell death, including caspases and proteins from the Bcl and Bax families. One organ where zinc is prominently involved in cell death is the brain, and cytotoxicity in consequence of ischemia or trauma involves the accumulation of free zinc. Rather than being a toxic metal ion, zinc is an essential trace element. Whereas intoxication by excessive exposure is rare, zinc deficiency is widespread and has a detrimental impact on growth, neuronal development, and immunity, and in severe cases its consequences are lethal. Zinc deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication.”, “author” : { “dropping-particle” : “”, “family” : “Plum”, “given” : “Laura M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rink”, “given” : “Lothar”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hajo”, “given” : “Haase”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Environmental Research and Public Health”, “id” : “ITEM-2”, “issue” : “4”, “issued” : { “date-parts” : “2010” }, “page” : “1342-1365”, “title” : “The essential toxin: Impact of zinc on human health”, “type” : “article-journal”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=f4d7d615-4621-40fd-95d3-73703581063e” } , “mendeley” : { “formattedCitation” : “(Lichten & Cousins, 2009; Plum et al., 2010)”, “plainTextFormattedCitation” : “(Lichten & Cousins, 2009; Plum et al., 2010)”, “previouslyFormattedCitation” : “(Lichten & Cousins, 2009; Plum et al., 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Lichten ; Cousins, 2009; Plum et al., 2010).

Figure 1: of role of zinc during cellular zinc homeostasis ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.3390/ijerph7041342”, “ISBN” : “1660-4601”, “ISSN” : “16604601”, “PMID” : “20617034”, “abstract” : “Compared to several other metal ions with similar chemical properties, zinc is relatively harmless. Only exposure to high doses has toxic effects, making acute zinc intoxication a rare event. In addition to acute intoxication, long-term, high-dose zinc supplementation interferes with the uptake of copper. Hence, many of its toxic effects are in fact due to copper deficiency. While systemic homeostasis and efficient regulatory mechanisms on the cellular level generally prevent the uptake of cytotoxic doses of exogenous zinc, endogenous zinc plays a significant role in cytotoxic events in single cells. Here, zinc influences apoptosis by acting on several molecular regulators of programmed cell death, including caspases and proteins from the Bcl and Bax families. One organ where zinc is prominently involved in cell death is the brain, and cytotoxicity in consequence of ischemia or trauma involves the accumulation of free zinc. Rather than being a toxic metal ion, zinc is an essential trace element. Whereas intoxication by excessive exposure is rare, zinc deficiency is widespread and has a detrimental impact on growth, neuronal development, and immunity, and in severe cases its consequences are lethal. Zinc deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication.”, “author” : { “dropping-particle” : “”, “family” : “Plum”, “given” : “Laura M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rink”, “given” : “Lothar”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hajo”, “given” : “Haase”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Environmental Research and Public Health”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2010” }, “page” : “1342-1365”, “title” : “The essential toxin: Impact of zinc on human health”, “type” : “article-journal”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=f4d7d615-4621-40fd-95d3-73703581063e” } , “mendeley” : { “formattedCitation” : “(Plum et al., 2010)”, “plainTextFormattedCitation” : “(Plum et al., 2010)”, “previouslyFormattedCitation” : “(Plum et al., 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Plum et al., 2010)
3.0 Health benefits of zinc
A. Zinc in immune system
Immune system needs zinc essential trace element to fight against infections due to viruses, bacteria, fungi and protozoa ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.autrev.2014.11.008”, “ISBN” : “1568-9972”, “ISSN” : “18730183”, “PMID” : “25462582”, “abstract” : “Zinc (Zn) nutritional importance has been known for a long time, but in the last decades its importance in immune modulation has arisen. This review aims at describing the mechanisms involved in the regulation of Zn homeostasis and their effects on the immune response focusing on those which are implicated in the physiopathology of rheumatoid arthritis. Zn functions as a modulator of the immune response through its availability, which is tightly regulated by several transporters and regulators. When this mechanism is disturbed, Zn availability is reduced, altering survival, proliferation and differentiation of the cells of different organs and systems and, in particular, cells of the immune system. Zn deficiency affects cells involved in both innate and adaptive immunity at the survival, proliferation and maturation levels. These cells include monocytes, polymorphonuclear-, natural killer-, T-, and B-cells. T cell functions and the balance between the different T helper cell subsets are particularly susceptible to changes in Zn status. While acute Zn deficiency causes a decrease in innate and adaptive immunity, chronic deficiency increases inflammation. During chronic deficiency, the production of pro-inflammatory cytokines increases, influencing the outcome of a large number of inflammatory diseases, including rheumatoid arthritis.”, “author” : { “dropping-particle” : “”, “family” : “Bonaventura”, “given” : “Paola”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Benedetti”, “given” : “Giulia”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Albaru00e8de”, “given” : “Francis”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Miossec”, “given” : “Pierre”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Autoimmunity Reviews”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2015” }, “page” : “277-285”, “title” : “Zinc and its role in immunity and inflammation”, “type” : “article-journal”, “volume” : “14” }, “uris” : “http://www.mendeley.com/documents/?uuid=7889bff7-6d3f-4a37-bf15-83245c6d6cb6” } , “mendeley” : { “formattedCitation” : “(Bonaventura, Benedetti, Albaru00e8de, & Miossec, 2015)”, “manualFormatting” : “(Bonaventura et al., 2015)”, “plainTextFormattedCitation” : “(Bonaventura, Benedetti, Albaru00e8de, & Miossec, 2015)”, “previouslyFormattedCitation” : “(Bonaventura, Benedetti, Albaru00e8de, & Miossec, 2015)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Bonaventura et al., 2015). Zinc-binding proteins, like metallothioneins (MTs) are from intra-cellular metal binding proteins which are present in all living things and they are important for the zinc effect in the immune system ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Stefanidou et al., 2006)”, “plainTextFormattedCitation” : “(Stefanidou et al., 2006)”, “previouslyFormattedCitation” : “(Stefanidou et al., 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Stefanidou et al., 2006). Without zinc, immune system cannot do their work to ensure that the body is not exposed to any pathogen. It can decrease lytic activity of natural killer cells, damage the natural killer T cell cytotoxicity and immune signalling, affects the neuroendocrine immune pathway and alters cytokine production in mast cells (Muzzioli et al.,2009; Mocchegianietal,2003; article 14). Moreover, zinc is one of the components that is needed in thymic hormones which commands and ease the process of lymphocyte maturation ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “See, stats, and : https : / / www . researchgate . net / publication / 277014212 A human Article CITATIONS 4 READS 1 , 028 3 , including : Some : organ Debjit HIPER 165 SEE Chiranjib Srikrupa 28 SEE All . The . All – text and , letting . Zinc is an essential nutrient for human health . Ensuring adequate levels of zinc intake should be a key component in efforts to reduce child illness , enhance physical growth and decrease mortality in developing countries . In spite of the proven benefits of adequate zinc nutrition , approximately 2 billion people still remain risk of zinc deficiency . Zinc is found in over 200 enzymes and hormones in mankind . It is a natural element found in all plants and animals , and is widely available in over – the – counter vitamin supplements . Zinc is essential to life . It is a natural element found in all plants and animals and plays a crucial part in the health of our skin , teeth , bones , hair , nails , muscles , nerves and brain function Zinc is essential for growth . It is used to control the enzymes that operate and renew the cells in our bodies . The formation of DNA , the basis of all life on our planet , would not be possible without zinc . Zinc deficiency was a major etiological factor in the syndrome of adolescent nutritional dwarfism , that had been identified mid – eastern countries . Zinc deficiency is an important public health problem , Nutritionists have been concerned that zinc deficiency affects large numbers of women and children in India and worldwide . In recent survey by WHO , zinc deficiency found most of the Indian population and Zinc supplement is used to commonly to enhance wound healing and treatment of pneumonia . Zinc gluconate lozenges , taken at the first sign of a common cold , reduce duration and symptom severity by 42% according to a 1992 study . Trace element zinc is important in maintaining the healthy growth of the human body , especially for infants and young children ‘ s growth and development .”, “author” : { “dropping-particle” : “”, “family” : “Bhowmik”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chiranjib”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Int. J. Pharm. Biomed. Sci.”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2010” }, “page” : “5-11”, “title” : “A potential medicinal importance of zinc in human health and chronic disease”, “type” : “article-journal”, “volume” : “1” }, “uris” : “http://www.mendeley.com/documents/?uuid=81621b14-ff97-4e2c-8fa3-2ae716da8b22” } , “mendeley” : { “formattedCitation” : “(Bhowmik & Chiranjib, 2010)”, “plainTextFormattedCitation” : “(Bhowmik & Chiranjib, 2010)”, “previouslyFormattedCitation” : “(Bhowmik & Chiranjib, 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Bhowmik ; Chiranjib, 2010). Basically, eating too little of zinc can impair the immune system making you more likely to get sick.
Sometimes there are other factors to consider that can affect whether or not Zinc requirements are met in the human body. These factors include diet consumed, climatic conditions, and existence of stress due to stress, trauma, parasitic infestations and infections ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Stefanidou et al., 2006)”, “plainTextFormattedCitation” : “(Stefanidou et al., 2006)”, “previouslyFormattedCitation” : “(Stefanidou et al., 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Stefanidou et al., 2006). When someone is sick with the flu, it is said that the immune system is able to fight the flu virus with the aid of zinc. People in contact with those who have viruses might get infected by them too. When the body is exposed to pathogens, phagocytosis starts to trap and kill them by producing reactive oxygen. This process usually occurs in innate immune system. Low concentration of zinc is means by decrease in phagocytosis process ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.autrev.2014.11.008”, “ISBN” : “1568-9972”, “ISSN” : “18730183”, “PMID” : “25462582”, “abstract” : “Zinc (Zn) nutritional importance has been known for a long time, but in the last decades its importance in immune modulation has arisen. This review aims at describing the mechanisms involved in the regulation of Zn homeostasis and their effects on the immune response focusing on those which are implicated in the physiopathology of rheumatoid arthritis. Zn functions as a modulator of the immune response through its availability, which is tightly regulated by several transporters and regulators. When this mechanism is disturbed, Zn availability is reduced, altering survival, proliferation and differentiation of the cells of different organs and systems and, in particular, cells of the immune system. Zn deficiency affects cells involved in both innate and adaptive immunity at the survival, proliferation and maturation levels. These cells include monocytes, polymorphonuclear-, natural killer-, T-, and B-cells. T cell functions and the balance between the different T helper cell subsets are particularly susceptible to changes in Zn status. While acute Zn deficiency causes a decrease in innate and adaptive immunity, chronic deficiency increases inflammation. During chronic deficiency, the production of pro-inflammatory cytokines increases, influencing the outcome of a large number of inflammatory diseases, including rheumatoid arthritis.”, “author” : { “dropping-particle” : “”, “family” : “Bonaventura”, “given” : “Paola”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Benedetti”, “given” : “Giulia”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Albaru00e8de”, “given” : “Francis”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Miossec”, “given” : “Pierre”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Autoimmunity Reviews”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2015” }, “page” : “277-285”, “title” : “Zinc and its role in immunity and inflammation”, “type” : “article-journal”, “volume” : “14” }, “uris” : “http://www.mendeley.com/documents/?uuid=360e9435-3a80-4c4c-996c-1b1cafe83314” } , “mendeley” : { “formattedCitation” : “(Bonaventura et al., 2015)”, “plainTextFormattedCitation” : “(Bonaventura et al., 2015)”, “previouslyFormattedCitation” : “(Bonaventura et al., 2015)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Bonaventura et al., 2015). Trace elements such as selenium, iron, copper, zinc and copper to zinc ratios could serve as a symptom of viral liver failure ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Science”, “given” : “Basic Medical”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Medical”, “given” : “Kaohsiung”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issued” : { “date-parts” : “2006” }, “page” : “15-23”, “title” : “Selenium , Iron , Copper , and Zinc Levels and Copper-to-Zinc Ratios in Serum of Patients at Different Stages of Viral Hepatic Diseases”, “type” : “article-journal”, “volume” : “109” }, “uris” : “http://www.mendeley.com/documents/?uuid=b71ef4bd-e1c9-48bf-8351-8e3833baeec3” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1111/1541-4337.12067”, “ISBN” : “1541-4337”, “ISSN” : “15414337”, “abstract” : “The importance of zinc was 1st reported for Aspergillus niger. It took over 75 y to realize that zinc is also an essential trace element for rats, and an additional 30 y went by before it was recognized that this was also true for humans. The adult body contains about 2 to 3 g of zinc. Zinc is found in organs, tissues, bones, fluids, and cells. It is essential for many physiological functions and plays a significant role in a number of enzyme actions in the living systems. Bioinformatics estimates report that 10% of the human proteome contains zinc-binding sites. Based on its role in such a plethora of cellular components, zinc has diverse biological functions from enzymatic catalysis to playing a crucial role in cellular neuronal systems. Thus, based on the various published studies and reports, it is pertinent to state that zinc is one of the most important essential trace metals in human nutrition and lifestyle. Its deficiency may severely affect the homeostasis of a biological system. This review compiles the role of zinc in prophylaxis/therapeutics and provides current information about its effect on living beings.”, “author” : { “dropping-particle” : “”, “family” : “Kaur”, “given” : “Kuljeet”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gupta”, “given” : “Rajiv”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Saraf”, “given” : “Shubhini A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Saraf”, “given” : “Shailendra K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Comprehensive Reviews in Food Science and Food Safety”, “id” : “ITEM-2”, “issue” : “4”, “issued” : { “date-parts” : “2014” }, “page” : “358-376”, “title” : “Zinc: The metal of life”, “type” : “article-journal”, “volume” : “13” }, “uris” : “http://www.mendeley.com/documents/?uuid=e52b2802-3140-4b13-9e18-9f2b7613c1f5” } , “mendeley” : { “formattedCitation” : “(Kaur, Gupta, Saraf, & Saraf, 2014; Science & Medical, 2006)”, “plainTextFormattedCitation” : “(Kaur, Gupta, Saraf, & Saraf, 2014; Science & Medical, 2006)”, “previouslyFormattedCitation” : “(Kaur, Gupta, Saraf, & Saraf, 2014; Science & Medical, 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Kaur, Gupta, Saraf, ; Saraf, 2014; Science ; Medical, 2006).

Innate immune system should begin first and then followed by an adaptive immune system. Adaptive immune system is related to the T lymphocyte and B lymphocyte. T lymphocyte is matured by thymulin with the aid of zinc. Thymulin is a non-apeptidic hormone produced by thymic epithelial cell, ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/sj.ejcn.1601479”, “ISBN” : “0954-3007 (Print)\r0954-3007 (Linking)”, “ISSN” : “14765640”, “PMID” : “12142956”, “abstract” : “It is well recognized that zinc is an essential trace element, influencing growth and affecting the development and integrity of the immune system. Research has begun to clarify the molecular mechanisms underlying the action of zinc on the immune function. It is clear that this trace element has a broad impact on key immunity mediators, such as enzymes, thymic peptides and cytokines, explaining the paramount importance of zinc’s status on the regulation of lymphoid cell activation, proliferation and apoptosis. Ongoing and future studies regarding the immunological status of zinc deficiency ‘at risk’ groups could lead to public health interventions with nutritional doses of zinc supplements to prevent alteration of the immune system and improve resistance to infections.”, “author” : { “dropping-particle” : “”, “family” : “Dardenne”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “European Journal of Clinical Nutrition”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2002” }, “page” : “S20-S23”, “title” : “Zinc and immune function”, “type” : “article-journal”, “volume” : “56” }, “uris” : “http://www.mendeley.com/documents/?uuid=6c7c04b3-d85a-4605-837c-816aaf91bbfa” } , “mendeley” : { “formattedCitation” : “(Dardenne, 2002)”, “plainTextFormattedCitation” : “(Dardenne, 2002)”, “previouslyFormattedCitation” : “(Dardenne, 2002)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Dardenne, 2002). It was known that after being deprived of zinc for too long, both human or animals are more susceptible to injuries that comes with oxidative stress ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Stefanidou et al., 2006)”, “plainTextFormattedCitation” : “(Stefanidou et al., 2006)”, “previouslyFormattedCitation” : “(Stefanidou et al., 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Stefanidou et al., 2006). Acrodermatitis enteropathica leads to zinc deficiency in humans and this is an autosomal genetic recessive defect of the zinc metabolism which then affects obstruction of zinc absorption ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “Zinc deficiency in pregnant experimental animals limits fetal growth and, if severe, causes teratogenic anomalies. Although the data from human studies are not consistent, similar outcomes have been observed and were associated with poor maternal zinc status. This paper reviews humans studies of zinc status and pregnancy outcome, describes the physiologic adjustments in zinc utilization during pregnancy to meet fetal needs while maintaining maternal status, and identifies dietary and environmental conditions that may override those physiologic adjustments and put the health of the mother and fetus at risk. Adjustments in intestinal zinc absorption appear to be the primary means by which zinc retention is increased to meet fetal demands. However, transfer of sufficient zinc to the fetus is dependent on maintenance of normal maternal serum zinc concentrations. Conditions that could interfere with zinc absorption include intake of cereal-based diets that are high in phytate, high intakes of supplemental iron, or any gastrointestinal disease. Conditions that may alter maternal plasma zinc concentrations and the transport of zinc to the fetus include smoking, alcohol abuse, and an acute stress response to infection or trauma. Supplemental zinc may be prudent for women with poor gastrointestinal function or with any of these conditions during pregnancy.\n”, “author” : { “dropping-particle” : “”, “family” : “King”, “given” : “Janet C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Am J Clin Nutr”, “id” : “ITEM-1”, “issue” : “5”, “issued” : { “date-parts” : “2000” }, “page” : “1334S-1343”, “title” : “Determinants of maternal zinc status during pregnancy”, “type” : “article-journal”, “volume” : “71” }, “uris” : “http://www.mendeley.com/documents/?uuid=bd705427-6d44-43ec-bf52-79ab5ddb2e77” } , “mendeley” : { “formattedCitation” : “(King, 2000)”, “plainTextFormattedCitation” : “(King, 2000)”, “previouslyFormattedCitation” : “(King, 2000)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(King, 2000).

Another reason to keep zinc levels in our body to be at a normal level is to prevent creating damaged homeostasis in our system. This is due to the defective platelet aggregation, a decrease in T-Cell number and the responsiveness of T-lymphocytes to phytomitogens ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Stefanidou et al., 2006)”, “plainTextFormattedCitation” : “(Stefanidou et al., 2006)”, “previouslyFormattedCitation” : “(Stefanidou et al., 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Stefanidou et al., 2006). In terms of ageing, one of the many roots causing immunological responses to decline is because neuroendocrine function in the body system is failing ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.arr.2006.06.001”, “author” : { “dropping-particle” : “”, “family” : “Mocchegiani”, “given” : “Eugenio”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Santarelli”, “given” : “Lory”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Costarelli”, “given” : “Laura”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cipriano”, “given” : “Catia”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Muti”, “given” : “Elisa”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Giacconi”, “given” : “Robertina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issued” : { “date-parts” : “2006” }, “page” : “281-309”, “title” : “Plasticity of neuroendocrine u2013 thymus interactions during ontogeny and ageing : Role of zinc and arginine”, “type” : “article-journal”, “volume” : “5” }, “uris” : “http://www.mendeley.com/documents/?uuid=1d14f627-30a2-463a-a561-5ca8dda7c4e9” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-2”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Mocchegiani et al., 2006; Stefanidou et al., 2006)”, “plainTextFormattedCitation” : “(Mocchegiani et al., 2006; Stefanidou et al., 2006)”, “previouslyFormattedCitation” : “(Mocchegiani et al., 2006; Stefanidou et al., 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Mocchegiani et al., 2006; Stefanidou et al., 2006) and increasing in apoptosis regulated by zinc ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Stefanidou et al., 2006)”, “plainTextFormattedCitation” : “(Stefanidou et al., 2006)”, “previouslyFormattedCitation” : “(Stefanidou et al., 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Stefanidou et al., 2006).

The abnormal occurrence of various infections and the existence of lymphopenia and lymphoid organ atrophy in malnourished children have been observed many times. The evidence gathered had concluded that the reason is due to zinc insufficiency which is then related to this type of immunodeficiency ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/sj.ejcn.1601479”, “ISBN” : “0954-3007 (Print)\r0954-3007 (Linking)”, “ISSN” : “14765640”, “PMID” : “12142956”, “abstract” : “It is well recognized that zinc is an essential trace element, influencing growth and affecting the development and integrity of the immune system. Research has begun to clarify the molecular mechanisms underlying the action of zinc on the immune function. It is clear that this trace element has a broad impact on key immunity mediators, such as enzymes, thymic peptides and cytokines, explaining the paramount importance of zinc’s status on the regulation of lymphoid cell activation, proliferation and apoptosis. Ongoing and future studies regarding the immunological status of zinc deficiency ‘at risk’ groups could lead to public health interventions with nutritional doses of zinc supplements to prevent alteration of the immune system and improve resistance to infections.”, “author” : { “dropping-particle” : “”, “family” : “Dardenne”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “European Journal of Clinical Nutrition”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2002” }, “page” : “S20-S23”, “title” : “Zinc and immune function”, “type” : “article-journal”, “volume” : “56” }, “uris” : “http://www.mendeley.com/documents/?uuid=6c7c04b3-d85a-4605-837c-816aaf91bbfa” } , “mendeley” : { “formattedCitation” : “(Dardenne, 2002)”, “plainTextFormattedCitation” : “(Dardenne, 2002)”, “previouslyFormattedCitation” : “(Dardenne, 2002)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Dardenne, 2002).

Much more diseases can be developed such as gastrointestinal disorders, renal disease, sickle cell anaemia, alcoholism, some cancer types, AIDS, burns and others ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Keen”, “given” : “Carl L”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issued” : { “date-parts” : “1990” }, “title” : “Zinc deficiency and immune function”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=aa0897fa-f5ba-4a78-a4ff-8db500617ac0” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1016/0192-0561(95)00064-9”, “ISSN” : “01920561”, “abstract” : “The inevitability of thymic involution in ageing has been opened to question by two recent findings. First, it has been demonstrated that the synthesis and/or secretion of one thymic factor, zinc-thymulin (Zn-FTS), is still present, although reduced, in humans over 90 yr of age and in mice over 24 months of age. The major defect resides in the zinc saturation of thymulin, rather than in the synthesis and secretion rate of the polypeptide by the thymus. Zinc pool is in fact reduced in old age. Thymic explants from old mice in vitro for a short period (6 h) produce nearly the same amount of thymulin as young thymuses, but the zinc-bound form is nearly absent. Zinc addition to the cultures fully recovers the defect. These findings clearly suggest that thymic involution is not an intrinsic and irreversible phenomenon, but is largely due to microenvironmental factors, among which zinc is crucial. u00a9 1995.”, “author” : { “dropping-particle” : “”, “family” : “Mocchegiani”, “given” : “Eugenio”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fabris”, “given” : “Nicola”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Immunopharmacology”, “id” : “ITEM-2”, “issue” : “9”, “issued” : { “date-parts” : “1995” }, “page” : “745-749”, “title” : “Age-related thymus involution: Zinc reverses in vitro the thymulin secretion defect”, “type” : “article-journal”, “volume” : “17” }, “uris” : “http://www.mendeley.com/documents/?uuid=745ff807-500c-4d3d-ad37-7b5484ee8dc7” }, { “id” : “ITEM-3”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Fraker”, “given” : “Pamela J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “King”, “given” : “Louis E”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Laakko”, “given” : “Tonya”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vollmer”, “given” : “Teresa L”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-3”, “issue” : “February”, “issued” : { “date-parts” : “2018” }, “page” : “1399-1406”, “title” : “Zinc and Health : Current Status and Future Directions The Dynamic Link between the Integrity of the Immune System”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=8b2175af-4846-4c22-968e-95f574accd0f” }, { “id” : “ITEM-4”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-4”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Fraker, King, Laakko, & Vollmer, 2018; Keen, 1990; Mocchegiani & Fabris, 1995; Stefanidou et al., 2006)”, “plainTextFormattedCitation” : “(Fraker, King, Laakko, & Vollmer, 2018; Keen, 1990; Mocchegiani & Fabris, 1995; Stefanidou et al., 2006)”, “previouslyFormattedCitation” : “(Fraker, King, Laakko, & Vollmer, 2018; Keen, 1990; Mocchegiani & Fabris, 1995; Stefanidou et al., 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Fraker, King, Laakko, ; Vollmer, 2018; Keen, 1990; Mocchegiani ; Fabris, 1995; Stefanidou et al., 2006). Appropriate zinc supplementation prescribed to those individuals could help in preventing damage towards their immune system and massively improve the resistance of a host to fight against the infections ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/sj.ejcn.1601479”, “ISBN” : “0954-3007 (Print)\r0954-3007 (Linking)”, “ISSN” : “14765640”, “PMID” : “12142956”, “abstract” : “It is well recognized that zinc is an essential trace element, influencing growth and affecting the development and integrity of the immune system. Research has begun to clarify the molecular mechanisms underlying the action of zinc on the immune function. It is clear that this trace element has a broad impact on key immunity mediators, such as enzymes, thymic peptides and cytokines, explaining the paramount importance of zinc’s status on the regulation of lymphoid cell activation, proliferation and apoptosis. Ongoing and future studies regarding the immunological status of zinc deficiency ‘at risk’ groups could lead to public health interventions with nutritional doses of zinc supplements to prevent alteration of the immune system and improve resistance to infections.”, “author” : { “dropping-particle” : “”, “family” : “Dardenne”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “European Journal of Clinical Nutrition”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2002” }, “page” : “S20-S23”, “title” : “Zinc and immune function”, “type” : “article-journal”, “volume” : “56” }, “uris” : “http://www.mendeley.com/documents/?uuid=6c7c04b3-d85a-4605-837c-816aaf91bbfa” } , “mendeley” : { “formattedCitation” : “(Dardenne, 2002)”, “plainTextFormattedCitation” : “(Dardenne, 2002)”, “previouslyFormattedCitation” : “(Dardenne, 2002)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Dardenne, 2002).

B. Zinc in brain
Transportation of zinc from blood to brain
Zinc is an important nutrient for brain which is supplied through brain barrier system that incorporates blood-brain and blood-cerebrospinal fluid barrier ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0165-0173(00)00044-8”, “ISBN” : “0028-3843 (Print)\n0028-3843 (Linking)”, “ISSN” : “01650173”, “PMID” : “11113504”, “abstract” : “Zinc, an essential nutrient, is supplied to the brain via both the blood-brain and blood-cerebrospinal fluid barriers. Zinc is most concentrated in the limbic system, i.e. the hippocampus and amygdala, zinc-containing glutaminergic neuron-rich areas. A large portion of zinc serves the function of zinc metalloproteins in neurons and glial cells. In zinc-containing glutaminergic neurons, vesicular zinc, probably ionic zinc, may serve as an endogenous neuromodulator in synaptic neurotransmission. Vesicular zinc is dynamically coupled to the electrophysiological activity of zinc-containing glutaminergic neurons. Dietary zinc deprivation may influence zinc homeostasis in the brain, resulting in brain dysfunction such as learning impairment. Excessive excitation of zinc-containing glutaminergic neurons causes a decrease in vesicular zinc, and the decrease might be associated with the susceptibility to seizure. Alteration of zinc levels released into the synaptic cleft may influence neurotransmission in zinc-containing glutaminergic synapses. Therefore, zinc homeostasis in the presynaptic vesicle is important for the function of zinc-containing glutaminergic neurons. (C) 2000 Elsevier Science B.V.”, “author” : { “dropping-particle” : “”, “family” : “Takeda”, “given” : “Atsushi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Brain Research Reviews”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2000” }, “page” : “137-148”, “title” : “Movement of zinc and its functional significance in the brain”, “type” : “article-journal”, “volume” : “34” }, “uris” : “http://www.mendeley.com/documents/?uuid=268e13d7-8108-48d3-a3cd-1ab9b26fa202” } , “mendeley” : { “formattedCitation” : “(Atsushi Takeda, 2000)”, “plainTextFormattedCitation” : “(Atsushi Takeda, 2000)”, “previouslyFormattedCitation” : “(Atsushi Takeda, 2000)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Atsushi Takeda, 2000). Blood brain barrier surface is greater than the surface of blood cerebrospinal fluid barrier. Zinc homeostasis occur in brain barrier and its variation may correspond to brain dysfunction and neurological diseases ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “The brain barrier system, i.e., the blood-brain and blood-cerebrospinal fluid barriers, is important for zinc homeostasis in the brain. Zinc is supplied to the brain via both barriers. A large portion of zinc serves as zinc metalloproteins in neurons and glial cells. Approximately 10% of the total zinc in the brain, probably ionic zinc, exists in the synaptic vesicles, and may serve as an endogenous neuromodulator in synaptic neurotransmission. The turnover of zinc in the brain is much slower than in peripheral tissues such as the liver. However, dietary zinc deprivation affects zinc homeostasis in the brain. Vesicular zinc-enriched regions, e.g., the hippocampus, are responsive to dietary zinc deprivation, which causes brain dysfunctions such as learning impairment and olfactory dysfunction. Olfactory recognition is reversibly disturbed by the chelation of zinc released from amygdalar neuron terminals. On the other hand, the susceptibility to epileptic seizures, which may decrease vesicular zinc, is also enhanced by zinc deficiency. Therefore, zinc homeostasis in the brain is closely related to neuronal activity. Even in adult animals and probably adult humans, adequate zinc supply is important for brain functions and prevention of neurological diseases.”, “author” : { “dropping-particle” : “”, “family” : “Takeda”, “given” : “A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “BioMetals”, “id” : “ITEM-1”, “issue” : “3-4”, “issued” : { “date-parts” : “2001” }, “page” : “343-351”, “title” : “Zinc homeostasis and functions in the brain”, “type” : “article-journal”, “volume” : “14” }, “uris” : “http://www.mendeley.com/documents/?uuid=438c09e0-a926-416c-82dd-91363338ca8a” } , “mendeley” : { “formattedCitation” : “(A Takeda, 2001)”, “plainTextFormattedCitation” : “(A Takeda, 2001)”, “previouslyFormattedCitation” : “(A Takeda, 2001)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(A Takeda, 2001). The brain is made up of limbic system which include the hippocampus, amygdalia and zinc-containing glutaminergic neuron-rich areas. Hippocampus have high concentration of zinc as grey matter(ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “The brain barrier system, i.e., the blood-brain and blood-cerebrospinal fluid barriers, is important for zinc homeostasis in the brain. Zinc is supplied to the brain via both barriers. A large portion of zinc serves as zinc metalloproteins in neurons and glial cells. Approximately 10% of the total zinc in the brain, probably ionic zinc, exists in the synaptic vesicles, and may serve as an endogenous neuromodulator in synaptic neurotransmission. The turnover of zinc in the brain is much slower than in peripheral tissues such as the liver. However, dietary zinc deprivation affects zinc homeostasis in the brain. Vesicular zinc-enriched regions, e.g., the hippocampus, are responsive to dietary zinc deprivation, which causes brain dysfunctions such as learning impairment and olfactory dysfunction. Olfactory recognition is reversibly disturbed by the chelation of zinc released from amygdalar neuron terminals. On the other hand, the susceptibility to epileptic seizures, which may decrease vesicular zinc, is also enhanced by zinc deficiency. Therefore, zinc homeostasis in the brain is closely related to neuronal activity. Even in adult animals and probably adult humans, adequate zinc supply is important for brain functions and prevention of neurological diseases.”, “author” : { “dropping-particle” : “”, “family” : “Takeda”, “given” : “A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “BioMetals”, “id” : “ITEM-1”, “issue” : “3-4”, “issued” : { “date-parts” : “2001” }, “page” : “343-351”, “title” : “Zinc homeostasis and functions in the brain”, “type” : “article-journal”, “volume” : “14” }, “uris” : “http://www.mendeley.com/documents/?uuid=438c09e0-a926-416c-82dd-91363338ca8a” } , “mendeley” : { “formattedCitation” : “(A Takeda, 2001)”, “manualFormatting” : “A Takeda, 2001)”, “plainTextFormattedCitation” : “(A Takeda, 2001)”, “previouslyFormattedCitation” : “(A Takeda, 2001)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }A Takeda, 2001). In contrast, brain stem, cerebellum and spinal have low amount of zinc concentration ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1385/MN:24:1-3:099”, “ISSN” : “08937648 (ISSN)”, “PMID” : “11831557”, “abstract” : “Zinc is one of the most abundant transition metals in the brain. A substantial fraction (10-15%) of brain zinc is located inside presynaptic vesicles of certain glutamatergic terminals in a free or loosely bound state. This vesicle zinc is released with neuronal activity or depolarization, probably serving physiologic functions. However, with excess release, as may occur in a variety of pathologic conditions, zinc may translocate to and accumulate in postsynaptic neurons, events which may contribute to selective neuronal cell death. Intracellular mechanisms of zinc neurotoxicity may include disturbances in energy metabolism, increases in oxidative stress, and activation of apoptosis cascades. Zinc inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and depletes nicotinamide adenine dinucleotide (NAD(+)) and adenosine triphosphate (ATP). On the other hand, zinc activates protein kinase C (PKC) and extracellular signal-regulated kinase (Erk-1/2), and induces NADPH oxidase; these events result in oxidative neuronal injury. Zinc can also trigger caspase activation and apoptosis via the p75(NTR) pathway. Interestingly, the converse-depletion of intracellular zinc-also induces neuronal death, but in this case, exclusively via classical apoptosis. In addition to the neurotoxic effect, zinc may contribute to the pathogenesis of chronic neurodegenerative disease. For example, in Alzheimer’s disease (AD), mature amyloid plaques, but not preamyloid deposits, are found to contain high levels of zinc, suggesting the role of zinc in the process of plaque maturation. Further insights into roles of zinc in brain diseases may help set a new direction toward the development of effective treatments.”, “author” : { “dropping-particle” : “”, “family” : “Koh”, “given” : “J Y”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Molecular neurobiology”, “id” : “ITEM-1”, “issue” : “1-3”, “issued” : { “date-parts” : “2001” }, “page” : “99-106”, “title” : “Zinc and disease of the brain.”, “type” : “article-journal”, “volume” : “24” }, “uris” : “http://www.mendeley.com/documents/?uuid=4471d4dd-c78d-400e-a03e-ae78e8e42a4e” } , “mendeley” : { “formattedCitation” : “(Koh, 2001)”, “plainTextFormattedCitation” : “(Koh, 2001)”, “previouslyFormattedCitation” : “(Koh, 2001)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Koh, 2001). Zinc binding affinity for ligands takes place in serum as the serum categorized into 3 fractions which is protein-bound form, low molecular weight ligand-bound form and free zinc ion. Zinc from blood must bind with protein such as histidine before they transport to DMT1 (divalent metal transporter) or zinc transporter in brain. Albumin is a massive component of exchangeable zinc and then followed by amino acid. Amino acid consists of histidine and cysteine.
After zinc enters the brain side, they must pass through neuron and glial cell before they transfer by zinc transporter such as DMT1. Neuron cell consist of two sites for zinc to go through which are cell body and neuron terminal. In neuron, zinc bind with protein to form zinc containing glutaminergic neurons which is taken up to presynaptic vesicles. It is believed that presynaptic vesicles are concentrated in hippocampal formation (Bush A.I et al, 1994;ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0165-0173(00)00044-8”, “ISBN” : “0028-3843 (Print)\n0028-3843 (Linking)”, “ISSN” : “01650173”, “PMID” : “11113504”, “abstract” : “Zinc, an essential nutrient, is supplied to the brain via both the blood-brain and blood-cerebrospinal fluid barriers. Zinc is most concentrated in the limbic system, i.e. the hippocampus and amygdala, zinc-containing glutaminergic neuron-rich areas. A large portion of zinc serves the function of zinc metalloproteins in neurons and glial cells. In zinc-containing glutaminergic neurons, vesicular zinc, probably ionic zinc, may serve as an endogenous neuromodulator in synaptic neurotransmission. Vesicular zinc is dynamically coupled to the electrophysiological activity of zinc-containing glutaminergic neurons. Dietary zinc deprivation may influence zinc homeostasis in the brain, resulting in brain dysfunction such as learning impairment. Excessive excitation of zinc-containing glutaminergic neurons causes a decrease in vesicular zinc, and the decrease might be associated with the susceptibility to seizure. Alteration of zinc levels released into the synaptic cleft may influence neurotransmission in zinc-containing glutaminergic synapses. Therefore, zinc homeostasis in the presynaptic vesicle is important for the function of zinc-containing glutaminergic neurons. (C) 2000 Elsevier Science B.V.”, “author” : { “dropping-particle” : “”, “family” : “Takeda”, “given” : “Atsushi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Brain Research Reviews”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2000” }, “page” : “137-148”, “title” : “Movement of zinc and its functional significance in the brain”, “type” : “article-journal”, “volume” : “34” }, “uris” : “http://www.mendeley.com/documents/?uuid=268e13d7-8108-48d3-a3cd-1ab9b26fa202” } , “mendeley” : { “formattedCitation” : “(Atsushi Takeda, 2000)”, “manualFormatting” : “Atsushi Takeda, 2000)”, “plainTextFormattedCitation” : “(Atsushi Takeda, 2000)”, “previouslyFormattedCitation” : “(Atsushi Takeda, 2000)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Atsushi Takeda, 2000). Zinc containing glutaminergic neurons in presynaptic vesicles are used as neuromodulator which is then transferred into postsynaptic vesicles by synaptic cleft. Synaptic cleft is located between presynaptic vesicle and postsynaptic vesicle.

Figure 2: Transportation of zinc from blood to neuron and glial cell (brainz)

Figure 3: Synaptic cleft in between presynaptic cell and postsynaptic cell (http://www.zoology.ubc.ca/~gardner/synapses%20-%20presynaptic.htm)

Zinc Toxicity
Zinc hardly goes through redox activity compared to other metals (Bertholf R.L et al, 1988; ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0165-0173(00)00044-8”, “ISBN” : “0028-3843 (Print)\n0028-3843 (Linking)”, “ISSN” : “01650173”, “PMID” : “11113504”, “abstract” : “Zinc, an essential nutrient, is supplied to the brain via both the blood-brain and blood-cerebrospinal fluid barriers. Zinc is most concentrated in the limbic system, i.e. the hippocampus and amygdala, zinc-containing glutaminergic neuron-rich areas. A large portion of zinc serves the function of zinc metalloproteins in neurons and glial cells. In zinc-containing glutaminergic neurons, vesicular zinc, probably ionic zinc, may serve as an endogenous neuromodulator in synaptic neurotransmission. Vesicular zinc is dynamically coupled to the electrophysiological activity of zinc-containing glutaminergic neurons. Dietary zinc deprivation may influence zinc homeostasis in the brain, resulting in brain dysfunction such as learning impairment. Excessive excitation of zinc-containing glutaminergic neurons causes a decrease in vesicular zinc, and the decrease might be associated with the susceptibility to seizure. Alteration of zinc levels released into the synaptic cleft may influence neurotransmission in zinc-containing glutaminergic synapses. Therefore, zinc homeostasis in the presynaptic vesicle is important for the function of zinc-containing glutaminergic neurons. (C) 2000 Elsevier Science B.V.”, “author” : { “dropping-particle” : “”, “family” : “Takeda”, “given” : “Atsushi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Brain Research Reviews”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2000” }, “page” : “137-148”, “title” : “Movement of zinc and its functional significance in the brain”, “type” : “article-journal”, “volume” : “34” }, “uris” : “http://www.mendeley.com/documents/?uuid=268e13d7-8108-48d3-a3cd-1ab9b26fa202” } , “mendeley” : { “formattedCitation” : “(Atsushi Takeda, 2000)”, “manualFormatting” : “Atsushi Takeda, 2000)”, “plainTextFormattedCitation” : “(Atsushi Takeda, 2000)”, “previouslyFormattedCitation” : “(Atsushi Takeda, 2000)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Atsushi Takeda, 2000). Excessive levels of zinc might be toxic to the brain as it can cause damage to the cell membranes, change enzyme specificity, disrupt cellular functions and destruct the structure of DNA. (Bruins et al. 2000;ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Daniels”, “given” : “Willie M U”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hendricks”, “given” : “Jacobus”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Salie”, “given” : “Ruduwaan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “Van”, “family” : “Rensburg”, “given” : “Susan J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issue” : “June”, “issued” : { “date-parts” : “2004” }, “page” : “79-88”, “title” : “A Mechanism for Zinc Toxicity in Neuroblastoma Cells”, “type” : “article-journal”, “volume” : “19” }, “uris” : “http://www.mendeley.com/documents/?uuid=a36385b3-9dcb-4a7d-9c76-2d3fa2b1376c” } , “mendeley” : { “formattedCitation” : “(Daniels, Hendricks, Salie, & Rensburg, 2004)”, “manualFormatting” : “Daniels, Hendricks, Salie, & Rensburg, 2004)”, “plainTextFormattedCitation” : “(Daniels, Hendricks, Salie, & Rensburg, 2004)”, “previouslyFormattedCitation” : “(Daniels, Hendricks, Salie, & Rensburg, 2004)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Daniels, Hendricks, Salie, ; Rensburg, 2004). Zinc toxicity occurs in neurotransmitter system which contain glutaminergic neurons. Glutamate transportation is modified by zinc that interrupt its removal in synaptic cleft which can cause neuronal death ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Daniels”, “given” : “Willie M U”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hendricks”, “given” : “Jacobus”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Salie”, “given” : “Ruduwaan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “Van”, “family” : “Rensburg”, “given” : “Susan J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issue” : “June”, “issued” : { “date-parts” : “2004” }, “page” : “79-88”, “title” : “A Mechanism for Zinc Toxicity in Neuroblastoma Cells”, “type” : “article-journal”, “volume” : “19” }, “uris” : “http://www.mendeley.com/documents/?uuid=a36385b3-9dcb-4a7d-9c76-2d3fa2b1376c” } , “mendeley” : { “formattedCitation” : “(Daniels et al., 2004)”, “plainTextFormattedCitation” : “(Daniels et al., 2004)”, “previouslyFormattedCitation” : “(Daniels et al., 2004)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Daniels et al., 2004). As mentioned earlier, synaptic cleft is in between presynaptic vesicle and postsynaptic vesicle. When presynaptic ending receives an electrical signal, it is decoded into chemical messages. The synaptic cleft receives the message and then send it to postsynaptic cleft.

Excessive amount of zinc can activate the formation of amyloid plaques in the brain (Huang X et al,2000; Kaiser J,1994; Lee J.Y,1999;ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0165-0173(00)00044-8”, “ISBN” : “0028-3843 (Print)\n0028-3843 (Linking)”, “ISSN” : “01650173”, “PMID” : “11113504”, “abstract” : “Zinc, an essential nutrient, is supplied to the brain via both the blood-brain and blood-cerebrospinal fluid barriers. Zinc is most concentrated in the limbic system, i.e. the hippocampus and amygdala, zinc-containing glutaminergic neuron-rich areas. A large portion of zinc serves the function of zinc metalloproteins in neurons and glial cells. In zinc-containing glutaminergic neurons, vesicular zinc, probably ionic zinc, may serve as an endogenous neuromodulator in synaptic neurotransmission. Vesicular zinc is dynamically coupled to the electrophysiological activity of zinc-containing glutaminergic neurons. Dietary zinc deprivation may influence zinc homeostasis in the brain, resulting in brain dysfunction such as learning impairment. Excessive excitation of zinc-containing glutaminergic neurons causes a decrease in vesicular zinc, and the decrease might be associated with the susceptibility to seizure. Alteration of zinc levels released into the synaptic cleft may influence neurotransmission in zinc-containing glutaminergic synapses. Therefore, zinc homeostasis in the presynaptic vesicle is important for the function of zinc-containing glutaminergic neurons. (C) 2000 Elsevier Science B.V.”, “author” : { “dropping-particle” : “”, “family” : “Takeda”, “given” : “Atsushi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Brain Research Reviews”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2000” }, “page” : “137-148”, “title” : “Movement of zinc and its functional significance in the brain”, “type” : “article-journal”, “volume” : “34” }, “uris” : “http://www.mendeley.com/documents/?uuid=268e13d7-8108-48d3-a3cd-1ab9b26fa202” } , “mendeley” : { “formattedCitation” : “(Atsushi Takeda, 2000)”, “manualFormatting” : “Atsushi Takeda, 2000)”, “plainTextFormattedCitation” : “(Atsushi Takeda, 2000)”, “previouslyFormattedCitation” : “(Atsushi Takeda, 2000)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Atsushi Takeda, 2000). Alzheimer’s disease is at risk if synapsis activity is in excess. (Frederickson,2005; ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s12263-013-0379-x”, “author” : { “dropping-particle” : “”, “family” : “Nuttall”, “given” : “Johnathan R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Oteiza”, “given” : “Patricia I”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issued” : { “date-parts” : “2014” }, “title” : “Zinc and the aging brain”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=03f325f8-77e6-4573-914d-bbcaabf8fe86” } , “mendeley” : { “formattedCitation” : “(Nuttall & Oteiza, 2014)”, “manualFormatting” : “Nuttall & Oteiza, 2014)”, “plainTextFormattedCitation” : “(Nuttall & Oteiza, 2014)”, “previouslyFormattedCitation” : “(Nuttall & Oteiza, 2014)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Nuttall & Oteiza, 2014). The accumulation of amyloid plaques usually found in Alzheimer’s disease brain. Alzheimer’s disease usually starts slowly and worsen over time. The major symptom is difficulty with language, easily getting lost, mood swings, demotivated and not managing selfcare. Excess of zinc also retards the amyloid precursor protein (APP) which diminishes the oxidation of iron that leads to neuronal accumulation of ferrous iron ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s12263-013-0379-x”, “author” : { “dropping-particle” : “”, “family” : “Nuttall”, “given” : “Johnathan R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Oteiza”, “given” : “Patricia I”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issued” : { “date-parts” : “2014” }, “title” : “Zinc and the aging brain”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=03f325f8-77e6-4573-914d-bbcaabf8fe86” } , “mendeley” : { “formattedCitation” : “(Nuttall & Oteiza, 2014)”, “plainTextFormattedCitation” : “(Nuttall & Oteiza, 2014)”, “previouslyFormattedCitation” : “(Nuttall & Oteiza, 2014)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Nuttall & Oteiza, 2014). The ferrous iron can increase the oxidative stress. In addition, neuronal cell death is the consequence of the stimulation of kinases by zinc which promotes the accumulation of Tau in neurofibrillary tangles(NFT). This leads to positive feedback of loop where calcium influx through N-methyl-D-aspartate-sensitive glutamate receptors (NMDAR).

Figure 4: diagram of excess of zinc in Alzheimer’s disease pathology ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s12263-013-0379-x”, “author” : { “dropping-particle” : “”, “family” : “Nuttall”, “given” : “Johnathan R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Oteiza”, “given” : “Patricia I”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issued” : { “date-parts” : “2014” }, “title” : “Zinc and the aging brain”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=03f325f8-77e6-4573-914d-bbcaabf8fe86” } , “mendeley” : { “formattedCitation” : “(Nuttall & Oteiza, 2014)”, “plainTextFormattedCitation” : “(Nuttall & Oteiza, 2014)”, “previouslyFormattedCitation” : “(Nuttall & Oteiza, 2014)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Nuttall ; Oteiza, 2014)
C. Zinc in Male Reproductive System
For men who plans to have a family, zinc is important for their reproductive system. Zinc is mostly found in the prostate gland ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1530/jrf.0.0990421”, “ISBN” : “0022-4251”, “ISSN” : “1470-1626”, “PMID” : “8107024”, “abstract” : “The concentrations of lead in blood and the concentrations of lead, cadmium and zinc in tissues were determined in various reproductive organs, liver and kidney removed at necropsy from 41 men who had died suddenly. None of the reproductive organs specifically accumulated lead and no significant correlation could be demonstrated between blood and organ concentrations or between concentrations and age, occupation or urban/rural background of the subject. Unlike lead, the tissue concentrations of cadmium increased with increasing age in all of the reproductive organs examined. Of these, the epididymides and seminal vesicles contained the highest concentrations. Whereas prostatic zinc also exhibited a significant age-dependent increase, the concentrations in the testes declined with age. The age-dependent increase in testicular cadmium did not become apparent until after the fourth decade, when any potentially deleterious impact on male fertility has less relevance. It is concluded that measurable amounts of lead and cadmium are present in all of the human reproductive organs but their organ and age distribution do not offer strong support for their involvement in the aetiology of male infertility or in the genesis of glandular neoplasms.”, “author” : { “dropping-particle” : “”, “family” : “Oldereid”, “given” : “N B”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Thomassen”, “given” : “Y”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Attramadal”, “given” : “A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Olaisen”, “given” : “B”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Purvis”, “given” : “K”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Reproduction & Fertility”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “1993” }, “page” : “421-425”, “title” : “Concentrations of lead, cadmium and zinc in the tissues of reproductive organs of men”, “type” : “article-journal”, “volume” : “99” }, “uris” : “http://www.mendeley.com/documents/?uuid=08822e9e-6339-4214-bc1b-618fbfe3734a” } , “mendeley” : { “formattedCitation” : “(Oldereid, Thomassen, Attramadal, Olaisen, & Purvis, 1993)”, “plainTextFormattedCitation” : “(Oldereid, Thomassen, Attramadal, Olaisen, & Purvis, 1993)”, “previouslyFormattedCitation” : “(Oldereid, Thomassen, Attramadal, Olaisen, & Purvis, 1993)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Oldereid, Thomassen, Attramadal, Olaisen, ; Purvis, 1993). It is a small size gland that is located in the pelvis which is in the middle of penis and bladder. Testicular development, sperm maturation and testosterone synthesis are dependent to zinc. Low testosterone and low concentration and mortality of sperm may be due to zinc deficiency. Low concentration of zinc can give a bad effect to prostate gland which leads to an infection (prostatis) where the size of prostate gland becomes swollen ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “See, stats, and : https : / / www . researchgate . net / publication / 277014212 A human Article CITATIONS 4 READS 1 , 028 3 , including : Some : organ Debjit HIPER 165 SEE Chiranjib Srikrupa 28 SEE All . The . All – text and , letting . Zinc is an essential nutrient for human health . Ensuring adequate levels of zinc intake should be a key component in efforts to reduce child illness , enhance physical growth and decrease mortality in developing countries . In spite of the proven benefits of adequate zinc nutrition , approximately 2 billion people still remain risk of zinc deficiency . Zinc is found in over 200 enzymes and hormones in mankind . It is a natural element found in all plants and animals , and is widely available in over – the – counter vitamin supplements . Zinc is essential to life . It is a natural element found in all plants and animals and plays a crucial part in the health of our skin , teeth , bones , hair , nails , muscles , nerves and brain function Zinc is essential for growth . It is used to control the enzymes that operate and renew the cells in our bodies . The formation of DNA , the basis of all life on our planet , would not be possible without zinc . Zinc deficiency was a major etiological factor in the syndrome of adolescent nutritional dwarfism , that had been identified mid – eastern countries . Zinc deficiency is an important public health problem , Nutritionists have been concerned that zinc deficiency affects large numbers of women and children in India and worldwide . In recent survey by WHO , zinc deficiency found most of the Indian population and Zinc supplement is used to commonly to enhance wound healing and treatment of pneumonia . Zinc gluconate lozenges , taken at the first sign of a common cold , reduce duration and symptom severity by 42% according to a 1992 study . Trace element zinc is important in maintaining the healthy growth of the human body , especially for infants and young children ‘ s growth and development .”, “author” : { “dropping-particle” : “”, “family” : “Bhowmik”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chiranjib”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Int. J. Pharm. Biomed. Sci.”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2010” }, “page” : “5-11”, “title” : “A potential medicinal importance of zinc in human health and chronic disease”, “type” : “article-journal”, “volume” : “1” }, “uris” : “http://www.mendeley.com/documents/?uuid=81621b14-ff97-4e2c-8fa3-2ae716da8b22” } , “mendeley” : { “formattedCitation” : “(Bhowmik & Chiranjib, 2010)”, “plainTextFormattedCitation” : “(Bhowmik & Chiranjib, 2010)”, “previouslyFormattedCitation” : “(Bhowmik & Chiranjib, 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Bhowmik ; Chiranjib, 2010). It is known as Benign Prostate Enlargement (BPE) whereby the prostate gland will press the bladder and urethra. When the urine passes through it, there will be difficulties in excreting but somehow it is not cancer. Male reproductive system is related to production of semen. Prostate gland is like a factory for production of semen. Semen is a mixture of sperm cells and other fluids. The fluid itself contains zinc which comes with selenium that is secreted by the prostate gland ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/humrep/13.8.2172”, “ISSN” : “0268-1161”, “PMID” : “9756291”, “abstract” : “The objective of the study was to obtain information on the concentration and distribution of selenium throughout the human male reproductive tract. Material was removed at autopsy from 41 men who had died suddenly and unexpectedly. Semen samples were also provided from 184 men attending an andrology clinic for fertility investigation and from 32 healthy volunteers. Significant positive correlations in the selenium concentration were demonstrated between the different reproductive organs, the testis having the highest concentrations. No correlation was found between the concentration of selenium in the genital organs and liver, kidney or blood, suggesting that its uptake and/or biochemical activity in the reproductive organs may be controlled by similar mechanisms not shared by the other organs. No significant age-dependent changes could be detected in tissue selenium concentrations. In a group of men under fertility investigation, a significant positive correlation was obtained between seminal plasma concentrations of selenium and concentrations of spermatozoa in the same ejaculate. A significant positive correlation between concentrations of zinc and selenium in the same ejaculates indicated that selenium may arise largely from the prostate gland.”, “author” : { “dropping-particle” : “”, “family” : “Oldereid”, “given” : “N B”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Thomassen”, “given” : “Y”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Purvis”, “given” : “K”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Human reproduction (Oxford, England)”, “id” : “ITEM-1”, “issue” : “8”, “issued” : { “date-parts” : “1998” }, “page” : “2172-6”, “title” : “Selenium in human male reproductive organs.”, “type” : “article-journal”, “volume” : “13” }, “uris” : “http://www.mendeley.com/documents/?uuid=8f5f64b8-e214-4b85-90e9-31acaf510fde” } , “mendeley” : { “formattedCitation” : “(Oldereid, Thomassen, & Purvis, 1998)”, “plainTextFormattedCitation” : “(Oldereid, Thomassen, & Purvis, 1998)”, “previouslyFormattedCitation” : “(Oldereid, Thomassen, & Purvis, 1998)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Oldereid, Thomassen, ; Purvis, 1998). Changes in amount of zinc in body parts can influence the sperm proliferation, maturation and viability ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Teliiman”, “given” : “Spomenka”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cvitkovi”, “given” : “Petar”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Jurasovit”, “given” : “Jasna”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pizent”, “given” : “Alica”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gavella”, “given” : “Mirjana”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Roit”, “given” : “Boris”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2000” }, “page” : “45-53”, “title” : “Semen Quality and Reproductive Endocrine Function in Relation to Biomarkers of Lead , Cadmium , Zinc , and Copper in Men”, “type” : “article-journal”, “volume” : “108” }, “uris” : “http://www.mendeley.com/documents/?uuid=2d0b97ff-3faa-497d-a504-60593c484a80” } , “mendeley” : { “formattedCitation” : “(Teliiman et al., 2000)”, “plainTextFormattedCitation” : “(Teliiman et al., 2000)”, “previouslyFormattedCitation” : “(Teliiman et al., 2000)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Teliiman et al., 2000). In addition, when the level of concentration of zinc is insufficient, it will prevent the production of luteinizing and follicle stimulating hormones from pituitary gland which is related to testosterone production ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “See, stats, and : https : / / www . researchgate . net / publication / 277014212 A human Article CITATIONS 4 READS 1 , 028 3 , including : Some : organ Debjit HIPER 165 SEE Chiranjib Srikrupa 28 SEE All . The . All – text and , letting . Zinc is an essential nutrient for human health . Ensuring adequate levels of zinc intake should be a key component in efforts to reduce child illness , enhance physical growth and decrease mortality in developing countries . In spite of the proven benefits of adequate zinc nutrition , approximately 2 billion people still remain risk of zinc deficiency . Zinc is found in over 200 enzymes and hormones in mankind . It is a natural element found in all plants and animals , and is widely available in over – the – counter vitamin supplements . Zinc is essential to life . It is a natural element found in all plants and animals and plays a crucial part in the health of our skin , teeth , bones , hair , nails , muscles , nerves and brain function Zinc is essential for growth . It is used to control the enzymes that operate and renew the cells in our bodies . The formation of DNA , the basis of all life on our planet , would not be possible without zinc . Zinc deficiency was a major etiological factor in the syndrome of adolescent nutritional dwarfism , that had been identified mid – eastern countries . Zinc deficiency is an important public health problem , Nutritionists have been concerned that zinc deficiency affects large numbers of women and children in India and worldwide . In recent survey by WHO , zinc deficiency found most of the Indian population and Zinc supplement is used to commonly to enhance wound healing and treatment of pneumonia . Zinc gluconate lozenges , taken at the first sign of a common cold , reduce duration and symptom severity by 42% according to a 1992 study . Trace element zinc is important in maintaining the healthy growth of the human body , especially for infants and young children ‘ s growth and development .”, “author” : { “dropping-particle” : “”, “family” : “Bhowmik”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chiranjib”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Int. J. Pharm. Biomed. Sci.”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2010” }, “page” : “5-11”, “title” : “A potential medicinal importance of zinc in human health and chronic disease”, “type” : “article-journal”, “volume” : “1” }, “uris” : “http://www.mendeley.com/documents/?uuid=81621b14-ff97-4e2c-8fa3-2ae716da8b22” } , “mendeley” : { “formattedCitation” : “(Bhowmik & Chiranjib, 2010)”, “plainTextFormattedCitation” : “(Bhowmik & Chiranjib, 2010)”, “previouslyFormattedCitation” : “(Bhowmik & Chiranjib, 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Bhowmik ; Chiranjib, 2010). Hormones plays a big role in the reproduction system and it can also affect the increase or decreasADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.3109/01485019708994883”, “ISBN” : “0148-5016 (Print)\r0148-5016 (Linking)”, “ISSN” : “01485016”, “PMID” : “9140621”, “abstract” : “The effects of marginal (MZD) and severe (SZD) zinc-deficient diets on testicular function and development were studied in rats maintained on dietary treatment for 6 weeks after weaning. SZD produced variable degrees of histological changes as compared with pair-fed controls, including a significant decrease in the diameter of seminiferous tubules (p < .05) with variable degree of maturation arrest in different stages of spermatogenesis. No significant histological changes were obtained in testes of MZD rats. MZD rats-exhibited significant decreases in serum levels of testosterone (62.6%, p < .001) and progesterone (18.2%, p < .05) with no changes in that of FSH or LH. SZD rats showed marked decreases in serum levels of testosterone (17.8-fold, p < .001) and progesterone (28.8%, p < .001), whereas FSH showed an increase (34.4%, p < .05) as compared with respective controls. In vitro acute stimulation by hCG on testicular tissue preparation obtained from MZD rats resulted in much less androgen production (sum of androstenedione, testosterone, and androstanediol) (72.4%, p < .001) as compared with controls. Testicular androgen contents (sum of androstenedione, testosterone, and androstanediol) decreased significantly in MZD and SZD rats, with the latter showing the greatest decrease. SZD rats were asospermic, whereas MZD rats exhibited marked decrease in sperm counts (by 22.9%, p < .05) as compared with respective controls. The results reflect a direct action of zinc deficiency on testicular steroidogenesis and strongly support the idea that hypogonadism of zinc deficiency results mainly from changes in testicular steroidogenesis or indirectly from Leydig cell failure.”, “author” : { “dropping-particle” : “”, “family” : “Hamdi”, “given” : “S. A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Nassif”, “given” : “O. I.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ardawi”, “given” : “M. S.M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Andrology”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “1997” }, “page” : “243-253”, “title” : “Effect of marginal or severe dietary zinc deficiency on testicular development and functions of the rat”, “type” : “article-journal”, “volume” : “38” }, “uris” : “http://www.mendeley.com/documents/?uuid=bd6f624f-702b-4e4e-b64e-aea484009ec0” } , “mendeley” : { “formattedCitation” : “(Hamdi, Nassif, & Ardawi, 1997)”, “plainTextFormattedCitation” : “(Hamdi, Nassif, & Ardawi, 1997)”, “previouslyFormattedCitation” : “(Hamdi, Nassif, & Ardawi, 1997)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Hamdi, Nassif, ; Ardawi, 1997)e of weight. Testicular development is important in the production of testosterone’s hormone. A study reported that testicular failure is related to zinc deficiency (Endre L. et al,1990;ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.3109/01485019708994883”, “ISBN” : “0148-5016 (Print)\r0148-5016 (Linking)”, “ISSN” : “01485016”, “PMID” : “9140621”, “abstract” : “The effects of marginal (MZD) and severe (SZD) zinc-deficient diets on testicular function and development were studied in rats maintained on dietary treatment for 6 weeks after weaning. SZD produced variable degrees of histological changes as compared with pair-fed controls, including a significant decrease in the diameter of seminiferous tubules (p < .05) with variable degree of maturation arrest in different stages of spermatogenesis. No significant histological changes were obtained in testes of MZD rats. MZD rats-exhibited significant decreases in serum levels of testosterone (62.6%, p < .001) and progesterone (18.2%, p < .05) with no changes in that of FSH or LH. SZD rats showed marked decreases in serum levels of testosterone (17.8-fold, p < .001) and progesterone (28.8%, p < .001), whereas FSH showed an increase (34.4%, p < .05) as compared with respective controls. In vitro acute stimulation by hCG on testicular tissue preparation obtained from MZD rats resulted in much less androgen production (sum of androstenedione, testosterone, and androstanediol) (72.4%, p < .001) as compared with controls. Testicular androgen contents (sum of androstenedione, testosterone, and androstanediol) decreased significantly in MZD and SZD rats, with the latter showing the greatest decrease. SZD rats were asospermic, whereas MZD rats exhibited marked decrease in sperm counts (by 22.9%, p < .05) as compared with respective controls. The results reflect a direct action of zinc deficiency on testicular steroidogenesis and strongly support the idea that hypogonadism of zinc deficiency results mainly from changes in testicular steroidogenesis or indirectly from Leydig cell failure.”, “author” : { “dropping-particle” : “”, “family” : “Hamdi”, “given” : “S. A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Nassif”, “given” : “O. I.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ardawi”, “given” : “M. S.M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Andrology”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “1997” }, “page” : “243-253”, “title” : “Effect of marginal or severe dietary zinc deficiency on testicular development and functions of the rat”, “type” : “article-journal”, “volume” : “38” }, “uris” : “http://www.mendeley.com/documents/?uuid=bd6f624f-702b-4e4e-b64e-aea484009ec0” } , “mendeley” : { “formattedCitation” : “(Hamdi et al., 1997)”, “manualFormatting” : “Hamdi et al., 1997)”, “plainTextFormattedCitation” : “(Hamdi et al., 1997)”, “previouslyFormattedCitation” : “(Hamdi et al., 1997)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Hamdi et al., 1997). This statement was proven after conducting the experiment on rats for 6 weeks where the result showed the concentration of testosterone and progesterone to decrease but increase in follicle stimulating hormone (FSH) serum. Severe zinc deficiency also depletes the production of normal germ cell which are dependent on Sertoli cell hormone stimulation (Dym M. et al,1971;Ressell L. et al,1987;ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.3109/01485019708994883”, “ISBN” : “0148-5016 (Print)\r0148-5016 (Linking)”, “ISSN” : “01485016”, “PMID” : “9140621”, “abstract” : “The effects of marginal (MZD) and severe (SZD) zinc-deficient diets on testicular function and development were studied in rats maintained on dietary treatment for 6 weeks after weaning. SZD produced variable degrees of histological changes as compared with pair-fed controls, including a significant decrease in the diameter of seminiferous tubules (p < .05) with variable degree of maturation arrest in different stages of spermatogenesis. No significant histological changes were obtained in testes of MZD rats. MZD rats-exhibited significant decreases in serum levels of testosterone (62.6%, p < .001) and progesterone (18.2%, p < .05) with no changes in that of FSH or LH. SZD rats showed marked decreases in serum levels of testosterone (17.8-fold, p < .001) and progesterone (28.8%, p < .001), whereas FSH showed an increase (34.4%, p < .05) as compared with respective controls. In vitro acute stimulation by hCG on testicular tissue preparation obtained from MZD rats resulted in much less androgen production (sum of androstenedione, testosterone, and androstanediol) (72.4%, p < .001) as compared with controls. Testicular androgen contents (sum of androstenedione, testosterone, and androstanediol) decreased significantly in MZD and SZD rats, with the latter showing the greatest decrease. SZD rats were asospermic, whereas MZD rats exhibited marked decrease in sperm counts (by 22.9%, p < .05) as compared with respective controls. The results reflect a direct action of zinc deficiency on testicular steroidogenesis and strongly support the idea that hypogonadism of zinc deficiency results mainly from changes in testicular steroidogenesis or indirectly from Leydig cell failure.”, “author” : { “dropping-particle” : “”, “family” : “Hamdi”, “given” : “S. A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Nassif”, “given” : “O. I.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ardawi”, “given” : “M. S.M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Andrology”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “1997” }, “page” : “243-253”, “title” : “Effect of marginal or severe dietary zinc deficiency on testicular development and functions of the rat”, “type” : “article-journal”, “volume” : “38” }, “uris” : “http://www.mendeley.com/documents/?uuid=bd6f624f-702b-4e4e-b64e-aea484009ec0” } , “mendeley” : { “formattedCitation” : “(Hamdi et al., 1997)”, “manualFormatting” : “Hamdi et al., 1997)”, “plainTextFormattedCitation” : “(Hamdi et al., 1997)”, “previouslyFormattedCitation” : “(Hamdi et al., 1997)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Hamdi et al., 1997). However, the failure in testicular growth are not only affected by the amount of zinc but it is also affected by protein and energy intake due to loss of appetite.

Based on the experiment conducted, severe zinc deficiency can weaken spermatogenesis. Spermatogenesis is a mechanism for production of sperm cell in testes by developing the germ cells in seminiferous tubules into haploid spermatozoa. Meanwhile, seminiferous tubules are shrunken and the weight of testicular is decreased.

Toxicity of zinc oxide nanoparticle in male reproductive system.

Zinc oxide nanoparticle (ZnONp) moves freely in the surroundings. It plays a role in various industries including in cosmetics, pigments, biosensors, bioimaging, drug delivery and antibacterial agents. Impairment of blood-testes barrier is the consequence from zinc oxide nanoparticle which decreases the expression of the gap junction proteins in Sertoli cells. Meanwhile, zinc oxide nanoparticle changes the structure of cell membrane and mitochondrial outer membrane of Sertoli cell in-order-to disrupt blood-testes barrier. It leads to an increase in the activity of reactive oxygen species or oxidative stress activity in Sertoli cell. Activation of oxidative stress cause secretion of cytokine to occur which can damage the blood-testes barrier. Blood-testes barrier is located in between Sertoli cells which isolates further developed stage of germ cells. (wikipedia)

Figure 5: blood-testis barrier in between sertoli cell(8). (https://en.wikipedia.org/wiki/Blood%E2%80%93testis_barrier#/media/File:Germinal_epithelium_testicle.svg)

Figure 6: schematic summary of mechanism of zinc oxide nanoparticle impact on
male reproductive system in Sertoli cell and spermatocyte ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.tiv.2016.05.017”, “ISSN” : “18793177”, “PMID” : “27247145”, “abstract” : “Environmental exposure to nanomaterials is inevitable as nanomaterials become part of our daily life, and as a result, nanotoxicity research is gaining attention. Most investigators focused on the effects of zinc oxide nanoparticles (ZnO NPs) on human health, while limited information was available on the male reproductive system. Herein, mouse Sertoli cell line (TM-4) and spermatocyte cell line (GC2-spd) were used as in vitro models to explore the reproductive effects of ZnO NPs at sublethal dose and its underlying mechanisms. Cells were treated with different concentrations of ZnO NPs. By cell viability assay, a dose of 8 u03bcg/mL was found as a sublethal dose and increased the ROS levels in both cells. The decreased glutathione level and increased MDA level were also found in ZnO NPs treated group. In TM4 cells, the expressions of BTB proteins (ZO-1, occludin, claudin-5, and connexin-43) were lower in the ZnO NPs group. The increased cell permeability and increased TNF-u03b1 secretion were also observed in ZnO NPs group. In GC2-spd cells, S phase arrest and DNA damage occurred in ZnO NPs group, which could be partially rescued by NAC. Our findings demonstrated that exposure to ZnO NPs induced ROS generation, caused DNA damage of germ cells, and down-regulated the expression of BTB proteins in Sertoli cells which could compromise the integrity of the blood-testis barrier. All these contributed to the male reproductive cytotoxic effects of ZnO NPs that could be partially rescued by anti-oxidants.”, “author” : { “dropping-particle” : “”, “family” : “Liu”, “given” : “Qian”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Xu”, “given” : “Cheng”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ji”, “given” : “Guixiang”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Liu”, “given” : “Hui”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Mo”, “given” : “Yiqun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tollerud”, “given” : “David J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gu”, “given” : “Aihua”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zhang”, “given” : “Qunwei”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Toxicology in Vitro”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2016” }, “page” : “131-138”, “publisher” : “Elsevier B.V.”, “title” : “Sublethal effects of zinc oxide nanoparticles on male reproductive cells”, “type” : “article-journal”, “volume” : “35” }, “uris” : “http://www.mendeley.com/documents/?uuid=288f5c31-e40a-4f1e-a645-e8fb0f77fb63” } , “mendeley” : { “formattedCitation” : “(Liu et al., 2016)”, “plainTextFormattedCitation” : “(Liu et al., 2016)”, “previouslyFormattedCitation” : “(Liu et al., 2016)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Liu et al., 2016)
It was reported that zinc oxide nanoparticles can lead to more production of oxidative stress and reactive oxygen species(ROS) generation (Bondareko al et.,2013;ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.tiv.2016.05.017”, “ISSN” : “18793177”, “PMID” : “27247145”, “abstract” : “Environmental exposure to nanomaterials is inevitable as nanomaterials become part of our daily life, and as a result, nanotoxicity research is gaining attention. Most investigators focused on the effects of zinc oxide nanoparticles (ZnO NPs) on human health, while limited information was available on the male reproductive system. Herein, mouse Sertoli cell line (TM-4) and spermatocyte cell line (GC2-spd) were used as in vitro models to explore the reproductive effects of ZnO NPs at sublethal dose and its underlying mechanisms. Cells were treated with different concentrations of ZnO NPs. By cell viability assay, a dose of 8 u03bcg/mL was found as a sublethal dose and increased the ROS levels in both cells. The decreased glutathione level and increased MDA level were also found in ZnO NPs treated group. In TM4 cells, the expressions of BTB proteins (ZO-1, occludin, claudin-5, and connexin-43) were lower in the ZnO NPs group. The increased cell permeability and increased TNF-u03b1 secretion were also observed in ZnO NPs group. In GC2-spd cells, S phase arrest and DNA damage occurred in ZnO NPs group, which could be partially rescued by NAC. Our findings demonstrated that exposure to ZnO NPs induced ROS generation, caused DNA damage of germ cells, and down-regulated the expression of BTB proteins in Sertoli cells which could compromise the integrity of the blood-testis barrier. All these contributed to the male reproductive cytotoxic effects of ZnO NPs that could be partially rescued by anti-oxidants.”, “author” : { “dropping-particle” : “”, “family” : “Liu”, “given” : “Qian”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Xu”, “given” : “Cheng”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ji”, “given” : “Guixiang”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Liu”, “given” : “Hui”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Mo”, “given” : “Yiqun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tollerud”, “given” : “David J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gu”, “given” : “Aihua”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zhang”, “given” : “Qunwei”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Toxicology in Vitro”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2016” }, “page” : “131-138”, “publisher” : “Elsevier B.V.”, “title” : “Sublethal effects of zinc oxide nanoparticles on male reproductive cells”, “type” : “article-journal”, “volume” : “35” }, “uris” : “http://www.mendeley.com/documents/?uuid=288f5c31-e40a-4f1e-a645-e8fb0f77fb63” } , “mendeley” : { “formattedCitation” : “(Liu et al., 2016)”, “manualFormatting” : “Liu et al., 2016)”, “plainTextFormattedCitation” : “(Liu et al., 2016)”, “previouslyFormattedCitation” : “(Liu et al., 2016)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Liu et al., 2016). DNA damage could also occur due to ROS generation which are caused by the present of zinc oxide nanoparticle (Cai et al.2009;Hackenbergh et al.,2010, Li et al.,2002;ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.tiv.2016.05.017”, “ISSN” : “18793177”, “PMID” : “27247145”, “abstract” : “Environmental exposure to nanomaterials is inevitable as nanomaterials become part of our daily life, and as a result, nanotoxicity research is gaining attention. Most investigators focused on the effects of zinc oxide nanoparticles (ZnO NPs) on human health, while limited information was available on the male reproductive system. Herein, mouse Sertoli cell line (TM-4) and spermatocyte cell line (GC2-spd) were used as in vitro models to explore the reproductive effects of ZnO NPs at sublethal dose and its underlying mechanisms. Cells were treated with different concentrations of ZnO NPs. By cell viability assay, a dose of 8 u03bcg/mL was found as a sublethal dose and increased the ROS levels in both cells. The decreased glutathione level and increased MDA level were also found in ZnO NPs treated group. In TM4 cells, the expressions of BTB proteins (ZO-1, occludin, claudin-5, and connexin-43) were lower in the ZnO NPs group. The increased cell permeability and increased TNF-u03b1 secretion were also observed in ZnO NPs group. In GC2-spd cells, S phase arrest and DNA damage occurred in ZnO NPs group, which could be partially rescued by NAC. Our findings demonstrated that exposure to ZnO NPs induced ROS generation, caused DNA damage of germ cells, and down-regulated the expression of BTB proteins in Sertoli cells which could compromise the integrity of the blood-testis barrier. All these contributed to the male reproductive cytotoxic effects of ZnO NPs that could be partially rescued by anti-oxidants.”, “author” : { “dropping-particle” : “”, “family” : “Liu”, “given” : “Qian”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Xu”, “given” : “Cheng”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ji”, “given” : “Guixiang”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Liu”, “given” : “Hui”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Mo”, “given” : “Yiqun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tollerud”, “given” : “David J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gu”, “given” : “Aihua”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zhang”, “given” : “Qunwei”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Toxicology in Vitro”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2016” }, “page” : “131-138”, “publisher” : “Elsevier B.V.”, “title” : “Sublethal effects of zinc oxide nanoparticles on male reproductive cells”, “type” : “article-journal”, “volume” : “35” }, “uris” : “http://www.mendeley.com/documents/?uuid=288f5c31-e40a-4f1e-a645-e8fb0f77fb63” } , “mendeley” : { “formattedCitation” : “(Liu et al., 2016)”, “manualFormatting” : “Liu et al., 2016)”, “plainTextFormattedCitation” : “(Liu et al., 2016)”, “previouslyFormattedCitation” : “(Liu et al., 2016)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Liu et al., 2016). Generating ROS also activates the production of trk-TNF-a pathway which disrupts blood-testes barrier.

Prostate Cancer
One of the factor that can cause prostate cancer is lack of accumulation of zinc in prostate gland which are located in the peripheral zone of prostate. Malignancy of prostate cell mostly occur in peripheral zone ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1186/1476-4598-5-17”, “ISBN” : “1476459851”, “ISSN” : “14764598”, “PMID” : “16700911”, “abstract” : “BACKGROUND: The genetic and molecular mechanisms responsible for and associated specifically with the development and progression of malignant prostate cells are largely unidentified. In addition, despite its implication in virtually all malignant cells, the role of altered cellular metabolism as an essential factor in prostate malignancy has been largely ignored. Moreover, the intermediary metabolism of normal prostate as well as malignant prostate cells is among the least studied and most poorly understood of all mammalian cells. Some important factors, especially the role of zinc, have been identified and implicated in the development and progression of prostate malignancy. In this review, we provide a current and updated integrated assessment of the relationships of intermediary metabolism in normal prostate and in prostate cancer. The experimental and clinical evidence that leads to the formulation of concepts of normal and malignant prostate metabolism is presented. The evidence for a concept of zinc as a tumor suppressor agent and Zip1 zinc transporter as a tumor-suppressor gene is described. RESULTS: The specialized function of the normal prostate glandular epithelium to produce and secrete enormously high levels of citrate involves and requires unique intermediary metabolism activities that are not generally associated with other normal mammalian cells. The accumulation of zinc by these cells is an essential factor in this unique metabolic relationship. In malignancy, the normal zinc-accumulating citrate-producing epithelial cells are metabolically transformed to citrate-oxidizing cells that lose the ability to accumulate zinc. A genetic alteration in the expression of ZIP1 zinc transporter is associated with this metabolic transformation. These genetic/metabolic relationships have important consequences on citrate-related metabolism, bioenergetics, cell proliferation and invasive capabilities of the malignant cells, which result in tumor-suppression characteristics. CONCLUSION: The genetic/metabolic relationships in normal prostate glandular epithelium are driven by the unique function to accumulate and secrete citrate. The genetic/metabolic transformation of the prostate malignant cells is driven by the metabolic/bioenergetic, growth/proliferative, and invasive/migration requirements of the malignant process. Zinc is critical to these relationships. An understanding of these genetic/metabolic relationships provides new directions and opportunu2026”, “author” : { “dropping-particle” : “”, “family” : “Costello”, “given” : “Leslie C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Franklin”, “given” : “Renty B.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Molecular Cancer”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2006” }, “page” : “1-13”, “title” : “The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: Connecting the dots”, “type” : “article-journal”, “volume” : “5” }, “uris” : “http://www.mendeley.com/documents/?uuid=0ced04c4-8fbc-495f-af56-4070cbeda410” } , “mendeley” : { “formattedCitation” : “(Costello & Franklin, 2006)”, “plainTextFormattedCitation” : “(Costello & Franklin, 2006)”, “previouslyFormattedCitation” : “(Costello & Franklin, 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Costello & Franklin, 2006). Usually, the zinc level and citrate level are depleted in early stage of malignancy development. Metabolic transformation is the transformation of citrate-oxidatives that can accumulate zinc into citrate-oxidatives that cannot accumulate zinc. When accumulation of zinc is decreased, m-aconitase activity will start to active ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1186/1476-4598-5-17”, “ISBN” : “1476459851”, “ISSN” : “14764598”, “PMID” : “16700911”, “abstract” : “BACKGROUND: The genetic and molecular mechanisms responsible for and associated specifically with the development and progression of malignant prostate cells are largely unidentified. In addition, despite its implication in virtually all malignant cells, the role of altered cellular metabolism as an essential factor in prostate malignancy has been largely ignored. Moreover, the intermediary metabolism of normal prostate as well as malignant prostate cells is among the least studied and most poorly understood of all mammalian cells. Some important factors, especially the role of zinc, have been identified and implicated in the development and progression of prostate malignancy. In this review, we provide a current and updated integrated assessment of the relationships of intermediary metabolism in normal prostate and in prostate cancer. The experimental and clinical evidence that leads to the formulation of concepts of normal and malignant prostate metabolism is presented. The evidence for a concept of zinc as a tumor suppressor agent and Zip1 zinc transporter as a tumor-suppressor gene is described. RESULTS: The specialized function of the normal prostate glandular epithelium to produce and secrete enormously high levels of citrate involves and requires unique intermediary metabolism activities that are not generally associated with other normal mammalian cells. The accumulation of zinc by these cells is an essential factor in this unique metabolic relationship. In malignancy, the normal zinc-accumulating citrate-producing epithelial cells are metabolically transformed to citrate-oxidizing cells that lose the ability to accumulate zinc. A genetic alteration in the expression of ZIP1 zinc transporter is associated with this metabolic transformation. These genetic/metabolic relationships have important consequences on citrate-related metabolism, bioenergetics, cell proliferation and invasive capabilities of the malignant cells, which result in tumor-suppression characteristics. CONCLUSION: The genetic/metabolic relationships in normal prostate glandular epithelium are driven by the unique function to accumulate and secrete citrate. The genetic/metabolic transformation of the prostate malignant cells is driven by the metabolic/bioenergetic, growth/proliferative, and invasive/migration requirements of the malignant process. Zinc is critical to these relationships. An understanding of these genetic/metabolic relationships provides new directions and opportunu2026”, “author” : { “dropping-particle” : “”, “family” : “Costello”, “given” : “Leslie C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Franklin”, “given” : “Renty B.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Molecular Cancer”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2006” }, “page” : “1-13”, “title” : “The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: Connecting the dots”, “type” : “article-journal”, “volume” : “5” }, “uris” : “http://www.mendeley.com/documents/?uuid=0ced04c4-8fbc-495f-af56-4070cbeda410” } , “mendeley” : { “formattedCitation” : “(Costello & Franklin, 2006)”, “plainTextFormattedCitation” : “(Costello & Franklin, 2006)”, “previouslyFormattedCitation” : “(Costello & Franklin, 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Costello & Franklin, 2006). Metabolic transformation also involves the transformation of neoplastic cell which activates the process of malignancy of prostate cell (Costello L.C. & Franklin R.B.,2006; Costello L.C. & Franklin R.B.,2012; Costello L.C. et al.,2015;ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Franklin”, “given” : “Renty B”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zou”, “given” : “Jing”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zheng”, “given” : “Yao”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Naslund”, “given” : “Michael J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Costello”, “given” : “Leslie C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2016” }, “page” : “1-4”, “title” : “Cancer and Clinical Research Prostate Tumor Growth in the Mouse Ectopic Xenograft Model : A Zinc ClinMed”, “type” : “article-journal”, “volume” : “3” }, “uris” : “http://www.mendeley.com/documents/?uuid=960bfce1-1fc3-4cde-9126-a638a97e1279” } , “mendeley” : { “formattedCitation” : “(Franklin, Zou, Zheng, Naslund, & Costello, 2016)”, “manualFormatting” : “Franklin, Zou, Zheng, Naslund, & Costello, 2016)”, “plainTextFormattedCitation” : “(Franklin, Zou, Zheng, Naslund, & Costello, 2016)”, “previouslyFormattedCitation” : “(Franklin, Zou, Zheng, Naslund, & Costello, 2016)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }Franklin, Zou, Zheng, Naslund, & Costello, 2016). When normal cell experience genetic transformation into neoplastic phenotype, it is then called as malignant cell. Neoplastic cell undergo transformation such as metabolic transformation to provide synthetic requirements of malignancy.

Figure 7: the concept of metabolic development of malignant cells ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1186/1476-4598-5-17”, “ISBN” : “1476459851”, “ISSN” : “14764598”, “PMID” : “16700911”, “abstract” : “BACKGROUND: The genetic and molecular mechanisms responsible for and associated specifically with the development and progression of malignant prostate cells are largely unidentified. In addition, despite its implication in virtually all malignant cells, the role of altered cellular metabolism as an essential factor in prostate malignancy has been largely ignored. Moreover, the intermediary metabolism of normal prostate as well as malignant prostate cells is among the least studied and most poorly understood of all mammalian cells. Some important factors, especially the role of zinc, have been identified and implicated in the development and progression of prostate malignancy. In this review, we provide a current and updated integrated assessment of the relationships of intermediary metabolism in normal prostate and in prostate cancer. The experimental and clinical evidence that leads to the formulation of concepts of normal and malignant prostate metabolism is presented. The evidence for a concept of zinc as a tumor suppressor agent and Zip1 zinc transporter as a tumor-suppressor gene is described. RESULTS: The specialized function of the normal prostate glandular epithelium to produce and secrete enormously high levels of citrate involves and requires unique intermediary metabolism activities that are not generally associated with other normal mammalian cells. The accumulation of zinc by these cells is an essential factor in this unique metabolic relationship. In malignancy, the normal zinc-accumulating citrate-producing epithelial cells are metabolically transformed to citrate-oxidizing cells that lose the ability to accumulate zinc. A genetic alteration in the expression of ZIP1 zinc transporter is associated with this metabolic transformation. These genetic/metabolic relationships have important consequences on citrate-related metabolism, bioenergetics, cell proliferation and invasive capabilities of the malignant cells, which result in tumor-suppression characteristics. CONCLUSION: The genetic/metabolic relationships in normal prostate glandular epithelium are driven by the unique function to accumulate and secrete citrate. The genetic/metabolic transformation of the prostate malignant cells is driven by the metabolic/bioenergetic, growth/proliferative, and invasive/migration requirements of the malignant process. Zinc is critical to these relationships. An understanding of these genetic/metabolic relationships provides new directions and opportunu2026”, “author” : { “dropping-particle” : “”, “family” : “Costello”, “given” : “Leslie C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Franklin”, “given” : “Renty B.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Molecular Cancer”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2006” }, “page” : “1-13”, “title” : “The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: Connecting the dots”, “type” : “article-journal”, “volume” : “5” }, “uris” : “http://www.mendeley.com/documents/?uuid=0ced04c4-8fbc-495f-af56-4070cbeda410” } , “mendeley” : { “formattedCitation” : “(Costello & Franklin, 2006)”, “plainTextFormattedCitation” : “(Costello & Franklin, 2006)”, “previouslyFormattedCitation” : “(Costello & Franklin, 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Costello & Franklin, 2006)

It is believed that when prostate malignancy occurs, the zinc uptake transporter (ZIP1) is inhibited. Inhibition of ZIP1 will reduce the amount of zinc and decrease the cell tumor suppressor in prostate. Every disease has their own treatment. Study reported that zinc ionophore can treat patient with prostate cancer. The experiment was conducted to prove zinc ionophore can suppress malignant cell of prostate by applying a suitable concentration on mice equivalent to that used in human without giving bad effects ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Franklin”, “given” : “Renty B”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zou”, “given” : “Jing”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zheng”, “given” : “Yao”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Naslund”, “given” : “Michael J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Costello”, “given” : “Leslie C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2016” }, “page” : “1-4”, “title” : “Cancer and Clinical Research Prostate Tumor Growth in the Mouse Ectopic Xenograft Model : A Zinc ClinMed”, “type” : “article-journal”, “volume” : “3” }, “uris” : “http://www.mendeley.com/documents/?uuid=960bfce1-1fc3-4cde-9126-a638a97e1279” } , “mendeley” : { “formattedCitation” : “(Franklin et al., 2016)”, “plainTextFormattedCitation” : “(Franklin et al., 2016)”, “previouslyFormattedCitation” : “(Franklin et al., 2016)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Franklin et al., 2016). Figure 8: diagram of malignant cell and advanced malignancy is treat with clioquinol which can increase uptake accumulation of zinc ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Franklin”, “given” : “Renty B”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zou”, “given” : “Jing”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zheng”, “given” : “Yao”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Naslund”, “given” : “Michael J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Costello”, “given” : “Leslie C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2016” }, “page” : “1-4”, “title” : “Cancer and Clinical Research Prostate Tumor Growth in the Mouse Ectopic Xenograft Model : A Zinc ClinMed”, “type” : “article-journal”, “volume” : “3” }, “uris” : “http://www.mendeley.com/documents/?uuid=960bfce1-1fc3-4cde-9126-a638a97e1279” } , “mendeley” : { “formattedCitation” : “(Franklin et al., 2016)”, “plainTextFormattedCitation” : “(Franklin et al., 2016)”, “previouslyFormattedCitation” : “(Franklin et al., 2016)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Franklin et al., 2016) https://en.wikipedia.org/wiki/Blood%E2%80%93testis_barrierD. Significance of Zinc for Skin
There are three important categories that are partially overlapped for skin functions which are morphogenesis, repair and maintenance and protection. Somehow, zinc is involved in all of the categories mentioned above, ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1111/j.1524-4725.2005.31729”, “ISBN” : “1076-0512 (Print) 1076-0512 (Linking)”, “ISSN” : “1076-0512”, “PMID” : “16029676”, “abstract” : “BACKGROUND: Zinc is known to have a critical role in overall human physiology, which likely explains many of its therapeutic uses for the last several thousand years. The specific roles zinc plays in skin health and function are less widely known yet are likely just as critical based on the manifestations of dietary zinc deprivation, which include moderate to severe dermatitis. OBJECTIVE: To provide a critical review of the scientific literature as to the physiologic importance of zinc to skin, the biochemical basis for these effects, and pharmacologic aspects of zinc therapeutics. RESULTS AND CONCLUSIONS: Skin is in a continual state of renewal, placing a high demand on zinc-based enzymes and proteins that direct this process. The importance of zinc physiologically is especially evident in studies of wound healing and inflammation reduction. During these processes, the high needs for zinc can be supplemented externally, generally increasing the rates of the natural processes. Topical zinc delivery involves the pharmacologic optimization of zinc delivery, often mediated by the solubility of the zinc material and interactions within the product matrix.”, “author” : { “dropping-particle” : “”, “family” : “Schwartz”, “given” : “James R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Marsh”, “given” : “Randall G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Draelos”, “given” : “Zoe Diana”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Dermatologic surgery : official publication for American Society for Dermatologic Surgery et al.”, “id” : “ITEM-1”, “issue” : “7 Pt 2”, “issued” : { “date-parts” : “2005” }, “page” : “837-847; discussion 847”, “title” : “Zinc and skin health: overview of physiology and pharmacology.”, “type” : “article-journal”, “volume” : “31” }, “uris” : “http://www.mendeley.com/documents/?uuid=5e422575-2464-44b0-a305-7302e6959b59” } , “mendeley” : { “formattedCitation” : “(Schwartz, Marsh, & Draelos, 2005)”, “manualFormatting” : “(Schwartz et al., 2005)”, “plainTextFormattedCitation” : “(Schwartz, Marsh, & Draelos, 2005)”, “previouslyFormattedCitation” : “(Schwartz, Marsh, & Draelos, 2005)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Schwartz et al., 2005). Zinc in the form of protein complexes are located intracellularly and in extracellularly matrix (ECM) within the epidermal and dermal tissues. There, zinc functions as a stabilizer of cell membranes and an essential cofactor. Additionally, zinc plays a big role in mitosis, migration and maturation,ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1111/j.1524-475X.2006.00179.x”, “ISBN” : “1524-475X”, “ISSN” : “1067-1927”, “PMID” : “17244314”, “abstract” : “Zinc is an essential trace element in the human body and its importance in health and disease is appreciated. It serves as a cofactor in numerous transcription factors and enzyme systems including zinc-dependent matrix metalloproteinases that augment autodebridement and keratinocyte migration during wound repair. Zinc confers resistance to epithelial apoptosis through cytoprotection against reactive oxygen species and bacterial toxins possibly through antioxidant activity of the cysteine-rich metallothioneins. Zinc deficiency of hereditary or dietary cause can lead to pathological changes and delayed wound healing. Oral zinc supplementation may be beneficial in treating zinc-deficient leg ulcer patients, but its therapeutic place in surgical patients needs further clarification. Topical administration of zinc appears to be superior to oral therapy due to its action in reducing superinfections and necrotic material via enhanced local defense systems and collagenolytic activity, and the sustained release of zinc ions that stimulates epithelialization of wounds in normozincemic individuals. Zinc oxide in paste bandages (Unna boot) protects and soothes inflamed peri-ulcer skin. Zinc is transported through the skin from these formulations, although the systemic effects seem insignificant. We present here the first comprehensive account of zinc in wound management in relation to current concepts of wound bed preparation and the wound-healing cascade. This review article suggests that topical zinc therapy is underappreciated even though clinical evidence emphasizes its importance in autodebridement, anti-infective action, and promotion of epithelialization.”, “author” : { “dropping-particle” : “”, “family” : “Lansdown”, “given” : “Alan B. G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Mirastschijski”, “given” : “Ursula”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Stubbs”, “given” : “Nicky”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Scanlon”, “given” : “Elizabeth”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “u00c5gren”, “given” : “Magnus S.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Wound Repair and Regeneration”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2007” }, “page” : “2-16”, “title” : “Zinc in wound healing: Theoretical, experimental, and clinical aspects”, “type” : “article-journal”, “volume” : “15” }, “uris” : “http://www.mendeley.com/documents/?uuid=86f7bd91-301c-4be6-bdb8-c39d63893836” } , “mendeley” : { “formattedCitation” : “(Lansdown, Mirastschijski, Stubbs, Scanlon, & u00c5gren, 2007)”, “manualFormatting” : “(Lansdown et al., 2007)”, “plainTextFormattedCitation” : “(Lansdown, Mirastschijski, Stubbs, Scanlon, & u00c5gren, 2007)”, “previouslyFormattedCitation” : “(Lansdown, Mirastschijski, Stubbs, Scanlon, & u00c5gren, 2007)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Lansdown et al., 2007).

Figure 9: An overview of the key functional steps in the wound-healing process of skin with an indication of the places and functions of zinc in this process ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1111/j.1524-4725.2005.31729”, “ISBN” : “1076-0512 (Print) 1076-0512 (Linking)”, “ISSN” : “1076-0512”, “PMID” : “16029676”, “abstract” : “BACKGROUND: Zinc is known to have a critical role in overall human physiology, which likely explains many of its therapeutic uses for the last several thousand years. The specific roles zinc plays in skin health and function are less widely known yet are likely just as critical based on the manifestations of dietary zinc deprivation, which include moderate to severe dermatitis. OBJECTIVE: To provide a critical review of the scientific literature as to the physiologic importance of zinc to skin, the biochemical basis for these effects, and pharmacologic aspects of zinc therapeutics. RESULTS AND CONCLUSIONS: Skin is in a continual state of renewal, placing a high demand on zinc-based enzymes and proteins that direct this process. The importance of zinc physiologically is especially evident in studies of wound healing and inflammation reduction. During these processes, the high needs for zinc can be supplemented externally, generally increasing the rates of the natural processes. Topical zinc delivery involves the pharmacologic optimization of zinc delivery, often mediated by the solubility of the zinc material and interactions within the product matrix.”, “author” : { “dropping-particle” : “”, “family” : “Schwartz”, “given” : “James R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Marsh”, “given” : “Randall G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Draelos”, “given” : “Zoe Diana”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Dermatologic surgery : official publication for American Society for Dermatologic Surgery et al.”, “id” : “ITEM-1”, “issue” : “7 Pt 2”, “issued” : { “date-parts” : “2005” }, “page” : “837-847; discussion 847”, “title” : “Zinc and skin health: overview of physiology and pharmacology.”, “type” : “article-journal”, “volume” : “31” }, “uris” : “http://www.mendeley.com/documents/?uuid=5e422575-2464-44b0-a305-7302e6959b59” } , “mendeley” : { “formattedCitation” : “(Schwartz et al., 2005)”, “plainTextFormattedCitation” : “(Schwartz et al., 2005)”, “previouslyFormattedCitation” : “(Schwartz et al., 2005)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Schwartz et al., 2005)
From the diagram above, we can observe that zinc and zinc-containing proteins plays a role in almost every step of cutaneous wound reparation. Zinc is involved during the mitigation of extracellular matrix, cell migration, protein synthesis and in reduction of inflammation ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1111/j.1524-4725.2005.31729”, “ISBN” : “1076-0512 (Print) 1076-0512 (Linking)”, “ISSN” : “1076-0512”, “PMID” : “16029676”, “abstract” : “BACKGROUND: Zinc is known to have a critical role in overall human physiology, which likely explains many of its therapeutic uses for the last several thousand years. The specific roles zinc plays in skin health and function are less widely known yet are likely just as critical based on the manifestations of dietary zinc deprivation, which include moderate to severe dermatitis. OBJECTIVE: To provide a critical review of the scientific literature as to the physiologic importance of zinc to skin, the biochemical basis for these effects, and pharmacologic aspects of zinc therapeutics. RESULTS AND CONCLUSIONS: Skin is in a continual state of renewal, placing a high demand on zinc-based enzymes and proteins that direct this process. The importance of zinc physiologically is especially evident in studies of wound healing and inflammation reduction. During these processes, the high needs for zinc can be supplemented externally, generally increasing the rates of the natural processes. Topical zinc delivery involves the pharmacologic optimization of zinc delivery, often mediated by the solubility of the zinc material and interactions within the product matrix.”, “author” : { “dropping-particle” : “”, “family” : “Schwartz”, “given” : “James R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Marsh”, “given” : “Randall G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Draelos”, “given” : “Zoe Diana”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Dermatologic surgery : official publication for American Society for Dermatologic Surgery et al.”, “id” : “ITEM-1”, “issue” : “7 Pt 2”, “issued” : { “date-parts” : “2005” }, “page” : “837-847; discussion 847”, “title” : “Zinc and skin health: overview of physiology and pharmacology.”, “type” : “article-journal”, “volume” : “31” }, “uris” : “http://www.mendeley.com/documents/?uuid=5e422575-2464-44b0-a305-7302e6959b59” } , “mendeley” : { “formattedCitation” : “(Schwartz et al., 2005)”, “plainTextFormattedCitation” : “(Schwartz et al., 2005)”, “previouslyFormattedCitation” : “(Schwartz et al., 2005)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Schwartz et al., 2005). Moreover, it is also used as a catalyst for enzymes that is in-charge of DNA replication, gene transcription and RNA. At a cellular level, zinc is important in order for cells to survive and at the end affecting signal transduction, transcription and replication ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1046/j.1365-4362.2002.01567.x”, “ISBN” : “0011-9059”, “ISSN” : “00119059”, “PMID” : “12358835”, “abstract” : “Antioxidants play a critical role in keeping skin healthy. The antioxidant benefits of vitamin C and E are well known, but the importance of the trace mineral, zinc, has been overlooked. This article reviews the evidence supporting zinc’s antioxidant role in protecting against free radical-induced oxidative damage. Zinc protects against UV radiation, enhances wound healing, contributes to immune and neuropsychiatric functions, and decreases the relative risk of cancer and cardiovascular disease. All body tissues contain zinc; in skin, it is five to six times more concentrated in the epidermis than the dermis. Zinc is required for the normal growth, development and function of mammals. It is an essential element of more than 200 metalloenzymes, including the antioxidant enzyme, superoxide dismutase, and affects their conformity, stability, and activity. Zinc also is important for the proper functioning of the immune system, and for glandular, reproductive and cell health. Abundant evidence demonstrates the antioxidant role of zinc. Topical zinc, in the form of divalent zinc ions, has been reported to provide antioxidant photoprotection for skin. Two antioxidant mechanisms have been proposed for zinc: zinc ions may replace redox active molecules, such as iron and copper, at critical sites in cell membranes and proteins; alternatively, zinc ions may induce the synthesis of metallothionein, sulfhydryl-rich proteins that protect against free radicals. No matter how they work, topical zinc ions may provide an important and helpful antioxidant defense for skin.”, “author” : { “dropping-particle” : “”, “family” : “Rostan”, “given” : “Elizabeth F.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “V.”, “family” : “Debuys”, “given” : “Holly”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Madey”, “given” : “Doren L.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pinnell”, “given” : “Sheldon R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Dermatology”, “id” : “ITEM-1”, “issue” : “9”, “issued” : { “date-parts” : “2002” }, “page” : “606-611”, “title” : “Evidence supporting zinc as an important antioxidant for skin”, “type” : “article-journal”, “volume” : “41” }, “uris” : “http://www.mendeley.com/documents/?uuid=0e2a0ce0-e4c7-4a66-8a7c-be0da802bb5d” } , “mendeley” : { “formattedCitation” : “(Rostan, Debuys, Madey, ; Pinnell, 2002)”, “manualFormatting” : “(Rostan et al.,2002)”, “plainTextFormattedCitation” : “(Rostan, Debuys, Madey, ; Pinnell, 2002)”, “previouslyFormattedCitation” : “(Rostan, Debuys, Madey, ; Pinnell, 2002)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Rostan et al.,2002). Other than that, marginal zinc status in body also induce the levels of lipid peroxidation in mitochochondrial and microsomal membranes and the osmotic fragility of erythrocyte membranes which has something to do with the human body’s skin ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s00204-005-0009-5”, “ISBN” : “0020400500”, “ISSN” : “03405761”, “PMID” : “16187101”, “abstract” : “Zinc (Zn) is one of the most important trace elements in the body and it is essential as a catalytic, structural and regulatory ion. It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing. Zinc-binding proteins (metallothioneins, MTs), are protective in situations of stress and in situations of exposure to toxic metals, infections and low Zn nutrition. Metallothioneins play a key role in Zn-related cell homeostasis due to their high affinity for Zn, which is in turn relevant against oxidative stress and immune responses, including natural killer (NK) cell activity and ageing, since NK activity and Zn ion bioavailability decrease in ageing. Physiological supplementation of Zn in ageing and in age-related degenerative diseases corrects immune defects, reduces infection relapse and prevents ageing. Zinc is not stored in the body and excess intakes result in reduced absorption and increased excretion. Nevertheless, there are cases of acute and chronic Zn poisoning.”, “author” : { “dropping-particle” : “”, “family” : “Stefanidou”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Maravelias”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dona”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spiliopoulou”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Toxicology”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “1-9”, “title” : “Zinc: A multipurpose trace element”, “type” : “article-journal”, “volume” : “80” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ac17188-e2b0-4ee4-9f85-52831d2ab045” } , “mendeley” : { “formattedCitation” : “(Stefanidou et al., 2006)”, “plainTextFormattedCitation” : “(Stefanidou et al., 2006)”, “previouslyFormattedCitation” : “(Stefanidou et al., 2006)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Stefanidou et al., 2006)
Based on Schwartz et al.,2005, improvements were observed when wounds were exposed to zinc. Direct application of products containing zinc oxide showed promising results as it improves leg ulcers and when tending to wounds that require dressings. As we all know, zinc is not only limited to oral supplementation. Those that are normally used are zinc sulfate and zinc oxides. Zinc sulfate are used in lotions to promote granulations of indolent ulcers and in aqueous solutions to reduce chronic inflammation in conjunctivitis. Zinc oxide on the other hand is mostly used in ointments, pastes and lotions that is used by many to control various skin problems as zinc oxides are a protective astringent and consist of antiseptic properties. Other than that, daily zinc supplements that consists of elemental zinc such as zinc sulfate and zinc gluconate are also recommended in order to speed up the wound healing process.
To top it off, zinc reduces the risk of cancer and cardiovascular diseases and protects skin from ultraviolet radiations. However, consuming calcium and zinc at the same time could prevent zinc absorption in the human body and so calcium and zinc supplements are not recommended to be taken at the same time, ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1046/j.1365-4362.2002.01567.x”, “ISBN” : “0011-9059”, “ISSN” : “00119059”, “PMID” : “12358835”, “abstract” : “Antioxidants play a critical role in keeping skin healthy. The antioxidant benefits of vitamin C and E are well known, but the importance of the trace mineral, zinc, has been overlooked. This article reviews the evidence supporting zinc’s antioxidant role in protecting against free radical-induced oxidative damage. Zinc protects against UV radiation, enhances wound healing, contributes to immune and neuropsychiatric functions, and decreases the relative risk of cancer and cardiovascular disease. All body tissues contain zinc; in skin, it is five to six times more concentrated in the epidermis than the dermis. Zinc is required for the normal growth, development and function of mammals. It is an essential element of more than 200 metalloenzymes, including the antioxidant enzyme, superoxide dismutase, and affects their conformity, stability, and activity. Zinc also is important for the proper functioning of the immune system, and for glandular, reproductive and cell health. Abundant evidence demonstrates the antioxidant role of zinc. Topical zinc, in the form of divalent zinc ions, has been reported to provide antioxidant photoprotection for skin. Two antioxidant mechanisms have been proposed for zinc: zinc ions may replace redox active molecules, such as iron and copper, at critical sites in cell membranes and proteins; alternatively, zinc ions may induce the synthesis of metallothionein, sulfhydryl-rich proteins that protect against free radicals. No matter how they work, topical zinc ions may provide an important and helpful antioxidant defense for skin.”, “author” : { “dropping-particle” : “”, “family” : “Rostan”, “given” : “Elizabeth F.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “V.”, “family” : “Debuys”, “given” : “Holly”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Madey”, “given” : “Doren L.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pinnell”, “given” : “Sheldon R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Dermatology”, “id” : “ITEM-1”, “issue” : “9”, “issued” : { “date-parts” : “2002” }, “page” : “606-611”, “title” : “Evidence supporting zinc as an important antioxidant for skin”, “type” : “article-journal”, “volume” : “41” }, “uris” : “http://www.mendeley.com/documents/?uuid=0e2a0ce0-e4c7-4a66-8a7c-be0da802bb5d” } , “mendeley” : { “formattedCitation” : “(Rostan et al., 2002)”, “plainTextFormattedCitation” : “(Rostan et al., 2002)”, “previouslyFormattedCitation” : “(Rostan et al., 2002)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Rostan et al., 2002)
E. The significance of zinc in pre-menstrual syndrome and during pregnancy
Effects of zinc in Pre-menstrual syndrome
Studies shows that low concentration of zinc in women can cause pre-menstrual
syndrome. Symptoms of pre-menstrual syndrome includes emotional, tension and fluid retention. These symptoms are experienced by women in the days right before menstruation. According to studies, PMS affects 50% of menstruating women, ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “See, stats, and : https : / / www . researchgate . net / publication / 277014212 A human Article CITATIONS 4 READS 1 , 028 3 , including : Some : organ Debjit HIPER 165 SEE Chiranjib Srikrupa 28 SEE All . The . All – text and , letting . Zinc is an essential nutrient for human health . Ensuring adequate levels of zinc intake should be a key component in efforts to reduce child illness , enhance physical growth and decrease mortality in developing countries . In spite of the proven benefits of adequate zinc nutrition , approximately 2 billion people still remain risk of zinc deficiency . Zinc is found in over 200 enzymes and hormones in mankind . It is a natural element found in all plants and animals , and is widely available in over – the – counter vitamin supplements . Zinc is essential to life . It is a natural element found in all plants and animals and plays a crucial part in the health of our skin , teeth , bones , hair , nails , muscles , nerves and brain function Zinc is essential for growth . It is used to control the enzymes that operate and renew the cells in our bodies . The formation of DNA , the basis of all life on our planet , would not be possible without zinc . Zinc deficiency was a major etiological factor in the syndrome of adolescent nutritional dwarfism , that had been identified mid – eastern countries . Zinc deficiency is an important public health problem , Nutritionists have been concerned that zinc deficiency affects large numbers of women and children in India and worldwide . In recent survey by WHO , zinc deficiency found most of the Indian population and Zinc supplement is used to commonly to enhance wound healing and treatment of pneumonia . Zinc gluconate lozenges , taken at the first sign of a common cold , reduce duration and symptom severity by 42% according to a 1992 study . Trace element zinc is important in maintaining the healthy growth of the human body , especially for infants and young children ‘ s growth and development .”, “author” : { “dropping-particle” : “”, “family” : “Bhowmik”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chiranjib”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Int. J. Pharm. Biomed. Sci.”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2010” }, “page” : “5-11”, “title” : “A potential medicinal importance of zinc in human health and chronic disease”, “type” : “article-journal”, “volume” : “1” }, “uris” : “http://www.mendeley.com/documents/?uuid=81621b14-ff97-4e2c-8fa3-2ae716da8b22” } , “mendeley” : { “formattedCitation” : “(Bhowmik ; Chiranjib, 2010)”, “plainTextFormattedCitation” : “(Bhowmik ; Chiranjib, 2010)”, “previouslyFormattedCitation” : “(Bhowmik ; Chiranjib, 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Bhowmik & Chiranjib, 2010). It is also said that intake of zinc that is about or more than 15 mg/day showed a decrease risk of having PMS (Nierenberg,2013). Zinc regulates the secretion of hormones and progesterone and so low concentrations of zinc leads to a reduction in secretion of progesterone and endorphins. Women facing PMS was found with lower levels of zinc during the luteul phase of menstruation. Moreover, deficiencies of this mineral also co-relates to symptoms that is related to moods such as depression and menstrual cramps (Nierenberg,2013). With the help of zinc, it can increase blood flow or diminish inflammation in the uterus, preventing muscle cramps (Tremblay, 2018). According to the University of Maryland Medical Center, it is recommended to take multivitamins containing zinc in order to lessen premenstrual syndrome.
Effects of zinc during pregnancy
Based on Roohani et al, 2013, reproductive events can be affected if a
pregnant woman is deficit of zinc, copper and magnesium. These reproductive events include infertility, pregnancy wastage, birth defects, pregnancy-induced hypertension, placental abruption, premature rupture membranes, fetal growth retardation, still birth and low birth weight. Sometimes birth defects can be identified before birth, at birth or in some cases later in infancy such as hearing defects or other kinds of defect ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1111/1541-4337.12067”, “ISBN” : “1541-4337”, “ISSN” : “15414337”, “abstract” : “The importance of zinc was 1st reported for Aspergillus niger. It took over 75 y to realize that zinc is also an essential trace element for rats, and an additional 30 y went by before it was recognized that this was also true for humans. The adult body contains about 2 to 3 g of zinc. Zinc is found in organs, tissues, bones, fluids, and cells. It is essential for many physiological functions and plays a significant role in a number of enzyme actions in the living systems. Bioinformatics estimates report that 10% of the human proteome contains zinc-binding sites. Based on its role in such a plethora of cellular components, zinc has diverse biological functions from enzymatic catalysis to playing a crucial role in cellular neuronal systems. Thus, based on the various published studies and reports, it is pertinent to state that zinc is one of the most important essential trace metals in human nutrition and lifestyle. Its deficiency may severely affect the homeostasis of a biological system. This review compiles the role of zinc in prophylaxis/therapeutics and provides current information about its effect on living beings.”, “author” : { “dropping-particle” : “”, “family” : “Kaur”, “given” : “Kuljeet”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gupta”, “given” : “Rajiv”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Saraf”, “given” : “Shubhini A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Saraf”, “given” : “Shailendra K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Comprehensive Reviews in Food Science and Food Safety”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2014” }, “page” : “358-376”, “title” : “Zinc: The metal of life”, “type” : “article-journal”, “volume” : “13” }, “uris” : “http://www.mendeley.com/documents/?uuid=e52b2802-3140-4b13-9e18-9f2b7613c1f5” } , “mendeley” : { “formattedCitation” : “(Kaur et al., 2014)”, “manualFormatting” : “(Kaur et al., 2014)”, “plainTextFormattedCitation” : “(Kaur et al., 2014)”, “previouslyFormattedCitation” : “(Kaur et al., 2014)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Kaur et al., 2014). Besides that, external defects of marginal status of zinc during pregnancy also affects the appearance of the child such as misshaped heads and fused or missing digits of the feet ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “Zinc deficiency in pregnant experimental animals limits fetal growth and, if severe, causes teratogenic anomalies. Although the data from human studies are not consistent, similar outcomes have been observed and were associated with poor maternal zinc status. This paper reviews humans studies of zinc status and pregnancy outcome, describes the physiologic adjustments in zinc utilization during pregnancy to meet fetal needs while maintaining maternal status, and identifies dietary and environmental conditions that may override those physiologic adjustments and put the health of the mother and fetus at risk. Adjustments in intestinal zinc absorption appear to be the primary means by which zinc retention is increased to meet fetal demands. However, transfer of sufficient zinc to the fetus is dependent on maintenance of normal maternal serum zinc concentrations. Conditions that could interfere with zinc absorption include intake of cereal-based diets that are high in phytate, high intakes of supplemental iron, or any gastrointestinal disease. Conditions that may alter maternal plasma zinc concentrations and the transport of zinc to the fetus include smoking, alcohol abuse, and an acute stress response to infection or trauma. Supplemental zinc may be prudent for women with poor gastrointestinal function or with any of these conditions during pregnancy.\n”, “author” : { “dropping-particle” : “”, “family” : “King”, “given” : “Janet C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Am J Clin Nutr”, “id” : “ITEM-1”, “issue” : “5”, “issued” : { “date-parts” : “2000” }, “page” : “1334S-1343”, “title” : “Determinants of maternal zinc status during pregnancy”, “type” : “article-journal”, “volume” : “71” }, “uris” : “http://www.mendeley.com/documents/?uuid=bd705427-6d44-43ec-bf52-79ab5ddb2e77” } , “mendeley” : { “formattedCitation” : “(King, 2000)”, “plainTextFormattedCitation” : “(King, 2000)”, “previouslyFormattedCitation” : “(King, 2000)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(King, 2000). The research looking into the effects of zinc on immune functions in a healthy pregnant woman showed that zinc induces the mitogenic influence on human lymphocytes exerting its greatest proliferative influence in concentrations which is more than those in normal human plasma. However, the proliferative responses of peripheral blood lymphocytes to zinc were reduced to the same level as the phytomitogen PHA. As pregnancy progresses, plasma level decreases and during birth, the micronutrient level of zinc induces together with the increase of metabolism in both mother and foetus ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Raimi, O.G., Falade, O. A., Folorunso, O. S. and Lawal”, “given” : “A. K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Department”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2012” }, “page” : “53-60”, “title” : “Zinc and iron levels in pregnancy : A review”, “type” : “article-journal”, “volume” : “22” }, “uris” : “http://www.mendeley.com/documents/?uuid=c1914ab0-d4c5-4cb8-9852-7c5798933139” } , “mendeley” : { “formattedCitation” : “(Raimi, O.G., Falade, O. A., Folorunso, O. S. and Lawal ; Department, 2012)”, “manualFormatting” : “(Raimi et al., 2012)”, “plainTextFormattedCitation” : “(Raimi, O.G., Falade, O. A., Folorunso, O. S. and Lawal ; Department, 2012)”, “previouslyFormattedCitation” : “(Raimi, O.G., Falade, O. A., Folorunso, O. S. and Lawal ; Department, 2012)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Raimi et al., 2012). Severe low intake of zinc gives impact to the duration of gestation which is the development of foetus and can lead to an increase of risk for preterm delivery ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1111/1541-4337.12067”, “ISBN” : “1541-4337”, “ISSN” : “15414337”, “abstract” : “The importance of zinc was 1st reported for Aspergillus niger. It took over 75 y to realize that zinc is also an essential trace element for rats, and an additional 30 y went by before it was recognized that this was also true for humans. The adult body contains about 2 to 3 g of zinc. Zinc is found in organs, tissues, bones, fluids, and cells. It is essential for many physiological functions and plays a significant role in a number of enzyme actions in the living systems. Bioinformatics estimates report that 10% of the human proteome contains zinc-binding sites. Based on its role in such a plethora of cellular components, zinc has diverse biological functions from enzymatic catalysis to playing a crucial role in cellular neuronal systems. Thus, based on the various published studies and reports, it is pertinent to state that zinc is one of the most important essential trace metals in human nutrition and lifestyle. Its deficiency may severely affect the homeostasis of a biological system. This review compiles the role of zinc in prophylaxis/therapeutics and provides current information about its effect on living beings.”, “author” : { “dropping-particle” : “”, “family” : “Kaur”, “given” : “Kuljeet”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gupta”, “given” : “Rajiv”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Saraf”, “given” : “Shubhini A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Saraf”, “given” : “Shailendra K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Comprehensive Reviews in Food Science and Food Safety”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2014” }, “page” : “358-376”, “title” : “Zinc: The metal of life”, “type” : “article-journal”, “volume” : “13” }, “uris” : “http://www.mendeley.com/documents/?uuid=e52b2802-3140-4b13-9e18-9f2b7613c1f5” } , “mendeley” : { “formattedCitation” : “(Kaur et al., 2014)”, “plainTextFormattedCitation” : “(Kaur et al., 2014)”, “previouslyFormattedCitation” : “(Kaur et al., 2014)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Kaur et al., 2014). During pregnancy, an additional of 100mg is needed as 57% of the zinc consumed is deposited in the foetus and 24% is used in the uterine muscle ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “Zinc deficiency in pregnant experimental animals limits fetal growth and, if severe, causes teratogenic anomalies. Although the data from human studies are not consistent, similar outcomes have been observed and were associated with poor maternal zinc status. This paper reviews humans studies of zinc status and pregnancy outcome, describes the physiologic adjustments in zinc utilization during pregnancy to meet fetal needs while maintaining maternal status, and identifies dietary and environmental conditions that may override those physiologic adjustments and put the health of the mother and fetus at risk. Adjustments in intestinal zinc absorption appear to be the primary means by which zinc retention is increased to meet fetal demands. However, transfer of sufficient zinc to the fetus is dependent on maintenance of normal maternal serum zinc concentrations. Conditions that could interfere with zinc absorption include intake of cereal-based diets that are high in phytate, high intakes of supplemental iron, or any gastrointestinal disease. Conditions that may alter maternal plasma zinc concentrations and the transport of zinc to the fetus include smoking, alcohol abuse, and an acute stress response to infection or trauma. Supplemental zinc may be prudent for women with poor gastrointestinal function or with any of these conditions during pregnancy.\n”, “author” : { “dropping-particle” : “”, “family” : “King”, “given” : “Janet C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Am J Clin Nutr”, “id” : “ITEM-1”, “issue” : “5”, “issued” : { “date-parts” : “2000” }, “page” : “1334S-1343”, “title” : “Determinants of maternal zinc status during pregnancy”, “type” : “article-journal”, “volume” : “71” }, “uris” : “http://www.mendeley.com/documents/?uuid=bd705427-6d44-43ec-bf52-79ab5ddb2e77” } , “mendeley” : { “formattedCitation” : “(King, 2000)”, “plainTextFormattedCitation” : “(King, 2000)”, “previouslyFormattedCitation” : “(King, 2000)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(King, 2000). This additional need can be fulfilled by increasing intake of zinc or adjusting zinc homeostasis. However, the adjustment of zinc homeostasis will be much more in women that takes up low intake of zinc in their diet. Based on King 2000, other factors such as smoking, alcohol abuse, acute maternal infections, strenuous exercise and high doses of supplemental iron can affect the capability to absorb or transport zinc to the foetus. Then, level of zinc in body also can influence zinc absorption as zinc deprived humans absorb zinc efficiently whereas those with high zinc diet does not absorb zinc well ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Roohani”, “given” : “Nazanin”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hurrel”, “given” : “Richard”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kelishadi”, “given” : “Roya”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Schulin”, “given” : “Rainer”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Research in Medical Science”, “id” : “ITEM-1”, “issue” : “February”, “issued” : { “date-parts” : “2013” }, “title” : “Zinc and its importance for human health_An integrative review”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=1242dbf7-9488-400a-ab1b-aea235ca221d” } , “mendeley” : { “formattedCitation” : “(Roohani, Hurrel, Kelishadi, ; Schulin, 2013)”, “plainTextFormattedCitation” : “(Roohani, Hurrel, Kelishadi, ; Schulin, 2013)”, “previouslyFormattedCitation” : “(Roohani, Hurrel, Kelishadi, ; Schulin, 2013)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Roohani, Hurrel, Kelishadi, & Schulin, 2013).
Another factor is the mechanism between copper and anti-copper action that prevents the intestinal absorption of copper and so those with Wilson’s disease should be given anti-copper therapy during pregnancy ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Editorial”, “given” : “S E E”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Page”, “given” : “O N”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Al”, “given” : “Brewer E T”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issued” : { “date-parts” : “1997” }, “page” : “364-370”, “title” : “Treatment of Wilson u2019 s Disease With Zinc . XVII : Treatment During Pregnancy”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=d6a4e572-776d-4f0e-91a2-96a021cabf2d” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1111/1541-4337.12067”, “ISBN” : “1541-4337”, “ISSN” : “15414337”, “abstract” : “The importance of zinc was 1st reported for Aspergillus niger. It took over 75 y to realize that zinc is also an essential trace element for rats, and an additional 30 y went by before it was recognized that this was also true for humans. The adult body contains about 2 to 3 g of zinc. Zinc is found in organs, tissues, bones, fluids, and cells. It is essential for many physiological functions and plays a significant role in a number of enzyme actions in the living systems. Bioinformatics estimates report that 10% of the human proteome contains zinc-binding sites. Based on its role in such a plethora of cellular components, zinc has diverse biological functions from enzymatic catalysis to playing a crucial role in cellular neuronal systems. Thus, based on the various published studies and reports, it is pertinent to state that zinc is one of the most important essential trace metals in human nutrition and lifestyle. Its deficiency may severely affect the homeostasis of a biological system. This review compiles the role of zinc in prophylaxis/therapeutics and provides current information about its effect on living beings.”, “author” : { “dropping-particle” : “”, “family” : “Kaur”, “given” : “Kuljeet”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gupta”, “given” : “Rajiv”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Saraf”, “given” : “Shubhini A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Saraf”, “given” : “Shailendra K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Comprehensive Reviews in Food Science and Food Safety”, “id” : “ITEM-2”, “issue” : “4”, “issued” : { “date-parts” : “2014” }, “page” : “358-376”, “title” : “Zinc: The metal of life”, “type” : “article-journal”, “volume” : “13” }, “uris” : “http://www.mendeley.com/documents/?uuid=e52b2802-3140-4b13-9e18-9f2b7613c1f5” } , “mendeley” : { “formattedCitation” : “(Editorial, Page, ; Al, 1997; Kaur et al., 2014)”, “plainTextFormattedCitation” : “(Editorial, Page, ; Al, 1997; Kaur et al., 2014)”, “previouslyFormattedCitation” : “(Editorial, Page, ; Al, 1997; Kaur et al., 2014)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Editorial, Page, & Al, 1997; Kaur et al., 2014)Most of the time iron supplements are given to pregnant women. If zinc supplements are also given, there’s a possibility that the influence of iron supplements towards zinc status will be reduced and at the end risking the effect of being deficient of both nutrients ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Brien”, “given” : “Kimberly O O”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zavaleta”, “given” : “Nelly”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Caulfield”, “given” : “Laura E”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Wen”, “given” : “Jianping”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Abrams”, “given” : “Steven A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-1”, “issue” : “April 2000”, “issued” : { “date-parts” : “2018” }, “page” : “2251-2255”, “title” : “Community and International Nutrition in Pregnant Peruvian Women 1 , 2”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=78e4bb12-c105-4205-9cb8-ae1ccd7472a7” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1111/1541-4337.12067”, “ISBN” : “1541-4337”, “ISSN” : “15414337”, “abstract” : “The importance of zinc was 1st reported for Aspergillus niger. It took over 75 y to realize that zinc is also an essential trace element for rats, and an additional 30 y went by before it was recognized that this was also true for humans. The adult body contains about 2 to 3 g of zinc. Zinc is found in organs, tissues, bones, fluids, and cells. It is essential for many physiological functions and plays a significant role in a number of enzyme actions in the living systems. Bioinformatics estimates report that 10% of the human proteome contains zinc-binding sites. Based on its role in such a plethora of cellular components, zinc has diverse biological functions from enzymatic catalysis to playing a crucial role in cellular neuronal systems. Thus, based on the various published studies and reports, it is pertinent to state that zinc is one of the most important essential trace metals in human nutrition and lifestyle. Its deficiency may severely affect the homeostasis of a biological system. This review compiles the role of zinc in prophylaxis/therapeutics and provides current information about its effect on living beings.”, “author” : { “dropping-particle” : “”, “family” : “Kaur”, “given” : “Kuljeet”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gupta”, “given” : “Rajiv”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Saraf”, “given” : “Shubhini A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Saraf”, “given” : “Shailendra K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Comprehensive Reviews in Food Science and Food Safety”, “id” : “ITEM-2”, “issue” : “4”, “issued” : { “date-parts” : “2014” }, “page” : “358-376”, “title” : “Zinc: The metal of life”, “type” : “article-journal”, “volume” : “13” }, “uris” : “http://www.mendeley.com/documents/?uuid=e52b2802-3140-4b13-9e18-9f2b7613c1f5” } , “mendeley” : { “formattedCitation” : “(Brien, Zavaleta, Caulfield, Wen, ; Abrams, 2018; Kaur et al., 2014)”, “plainTextFormattedCitation” : “(Brien, Zavaleta, Caulfield, Wen, ; Abrams, 2018; Kaur et al., 2014)”, “previouslyFormattedCitation” : “(Brien, Zavaleta, Caulfield, Wen, ; Abrams, 2018; Kaur et al., 2014)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Brien, Zavaleta, Caulfield, Wen, & Abrams, 2018; Kaur et al., 2014).

In terms of lactation, those who started pregnancy with a marginal zinc status are usually zinc deficient as fetal growth requires an abundant concentration of zinc. So, these mothers will lack zinc in their system and it affects the level of zinc in their breast milk ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.4172/2161-0495.S3-001”, “ISSN” : “21610495”, “abstract” : “The human body has an elaborate system for managing and regulating the amount of key trace metals circulating in blood and stored in cells. Nutrient metals from our diet are incorporated into blood if blood levels are depleted, transported into cells if cellular levels are inadequate, or excreted if blood and cell levels are sufficient or overloaded. When this system fails to function properly, abnormal levels and ratios of trace metals can develop. One of the most common trace-metal imbalances is elevated copper and depressed zinc. The ratio of copper to zinc is clinically more important than the concentration of either of these trace metals 1.”, “author” : { “dropping-particle” : “”, “family” : “Osredkar”, “given” : “Josko”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Toxicology”, “id” : “ITEM-1”, “issue” : “01”, “issued” : { “date-parts” : “2011” }, “title” : “Copper and Zinc, Biological Role and Significance of Copper/Zinc Imbalance”, “type” : “article-journal”, “volume” : “s3” }, “uris” : “http://www.mendeley.com/documents/?uuid=c6c5c2a6-a018-4b9a-92ee-cae9eb3343da” } , “mendeley” : { “formattedCitation” : “(Osredkar, 2011)”, “plainTextFormattedCitation” : “(Osredkar, 2011)”, “previouslyFormattedCitation” : “(Osredkar, 2011)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Osredkar, 2011). Lactation describes the secretion of milk from the mammary glands and the duration when a mother lactates to feed her young. Premature infants are more susceptible to evolve zinc deficiency compared to a full-term infant as they have insufficient body storage for zinc and their ability to absorb zinc from the gut is defective. Generally, younger children require more nutrients as it is a critical stage for growth and so they are at risk of zinc deficiency. The first few months, babies require sufficient zinc from their mothers which is through breast feeding and then after that they can be fed by complementary foods containing absorbable zinc ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Roohani”, “given” : “Nazanin”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hurrel”, “given” : “Richard”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kelishadi”, “given” : “Roya”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Schulin”, “given” : “Rainer”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Research in Medical Science”, “id” : “ITEM-1”, “issue” : “February”, “issued” : { “date-parts” : “2013” }, “title” : “Zinc and its importance for human health_An integrative review”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=1242dbf7-9488-400a-ab1b-aea235ca221d” } , “mendeley” : { “formattedCitation” : “(Roohani et al., 2013)”, “manualFormatting” : “(Roohani et al., 2013)”, “plainTextFormattedCitation” : “(Roohani et al., 2013)”, “previouslyFormattedCitation” : “(Roohani et al., 2013)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Roohani et al., 2013).

As woman ages, the zinc status in their body decreases because they tend to eat less and the food they eat does not really have a large concentration of Zinc. Additionally, excess estrogen reduces zinc status. Zinc is needed at this point in order to slow down the progression of the disorder of retina ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “abstract” : “See, stats, and : https : / / www . researchgate . net / publication / 277014212 A human Article CITATIONS 4 READS 1 , 028 3 , including : Some : organ Debjit HIPER 165 SEE Chiranjib Srikrupa 28 SEE All . The . All – text and , letting . Zinc is an essential nutrient for human health . Ensuring adequate levels of zinc intake should be a key component in efforts to reduce child illness , enhance physical growth and decrease mortality in developing countries . In spite of the proven benefits of adequate zinc nutrition , approximately 2 billion people still remain risk of zinc deficiency . Zinc is found in over 200 enzymes and hormones in mankind . It is a natural element found in all plants and animals , and is widely available in over – the – counter vitamin supplements . Zinc is essential to life . It is a natural element found in all plants and animals and plays a crucial part in the health of our skin , teeth , bones , hair , nails , muscles , nerves and brain function Zinc is essential for growth . It is used to control the enzymes that operate and renew the cells in our bodies . The formation of DNA , the basis of all life on our planet , would not be possible without zinc . Zinc deficiency was a major etiological factor in the syndrome of adolescent nutritional dwarfism , that had been identified mid – eastern countries . Zinc deficiency is an important public health problem , Nutritionists have been concerned that zinc deficiency affects large numbers of women and children in India and worldwide . In recent survey by WHO , zinc deficiency found most of the Indian population and Zinc supplement is used to commonly to enhance wound healing and treatment of pneumonia . Zinc gluconate lozenges , taken at the first sign of a common cold , reduce duration and symptom severity by 42% according to a 1992 study . Trace element zinc is important in maintaining the healthy growth of the human body , especially for infants and young children ‘ s growth and development .”, “author” : { “dropping-particle” : “”, “family” : “Bhowmik”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chiranjib”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Int. J. Pharm. Biomed. Sci.”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2010” }, “page” : “5-11”, “title” : “A potential medicinal importance of zinc in human health and chronic disease”, “type” : “article-journal”, “volume” : “1” }, “uris” : “http://www.mendeley.com/documents/?uuid=81621b14-ff97-4e2c-8fa3-2ae716da8b22” } , “mendeley” : { “formattedCitation” : “(Bhowmik & Chiranjib, 2010)”, “plainTextFormattedCitation” : “(Bhowmik & Chiranjib, 2010)”, “previouslyFormattedCitation” : “(Bhowmik & Chiranjib, 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Bhowmik & Chiranjib, 2010).
4.0 Effect of high concentrations of zinc to human body
Zinc is type of mineral which must be taken in small amounts for good health as taking too much also has its downfall. There are three ways where zinc could have entered the human body which are through inhalation, through skin or through ingestion. Humans could be exposed to zinc-containing smoke especially when they are working or involved in the industrial processes like galvanization. Other than that, military smoke bombs consist of zinc oxide or zinc chloride that could be harmful to human when inhaled. Soldiers are usually the first to be exposed when it comes to smoke bombs. In some cases, soldiers could develop Adult Respiratory Distress Syndrome (ARDDS) and without proper treatment, it could lead to a certain death, ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.3390/ijerph7041342”, “ISBN” : “1660-4601”, “ISSN” : “16604601”, “PMID” : “20617034”, “abstract” : “Compared to several other metal ions with similar chemical properties, zinc is relatively harmless. Only exposure to high doses has toxic effects, making acute zinc intoxication a rare event. In addition to acute intoxication, long-term, high-dose zinc supplementation interferes with the uptake of copper. Hence, many of its toxic effects are in fact due to copper deficiency. While systemic homeostasis and efficient regulatory mechanisms on the cellular level generally prevent the uptake of cytotoxic doses of exogenous zinc, endogenous zinc plays a significant role in cytotoxic events in single cells. Here, zinc influences apoptosis by acting on several molecular regulators of programmed cell death, including caspases and proteins from the Bcl and Bax families. One organ where zinc is prominently involved in cell death is the brain, and cytotoxicity in consequence of ischemia or trauma involves the accumulation of free zinc. Rather than being a toxic metal ion, zinc is an essential trace element. Whereas intoxication by excessive exposure is rare, zinc deficiency is widespread and has a detrimental impact on growth, neuronal development, and immunity, and in severe cases its consequences are lethal. Zinc deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication.”, “author” : { “dropping-particle” : “”, “family” : “Plum”, “given” : “Laura M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rink”, “given” : “Lothar”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hajo”, “given” : “Haase”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Environmental Research and Public Health”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2010” }, “page” : “1342-1365”, “title” : “The essential toxin: Impact of zinc on human health”, “type” : “article-journal”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=f4d7d615-4621-40fd-95d3-73703581063e” } , “mendeley” : { “formattedCitation” : “(Plum et al., 2010)”, “plainTextFormattedCitation” : “(Plum et al., 2010)”, “previouslyFormattedCitation” : “(Plum et al., 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Plum et al., 2010). Being exposed to the smoke containing zinc oxide during the smelting or welding of zinc can also lead to Metal Fume Fever (MFF). However, the effect is not as life threatening and the respiratory effects will go away after a while.
In terms of dermal exposure, there are no proper evidence that it is harmful to the skin as lotions, ointments and other products consists of zinc substance.

Zinc ingestion does not affect the human body. However, zinc sulphate is toxic for the body. Additionally, too much of zinc intake could reduce the concentration of copper in the body. The recommended daily intake of zinc is roughly about 15 mg/day ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0753-3322(03)00081-7”, “ISBN” : “0753-3322”, “ISSN” : “07533322”, “PMID” : “14652165”, “abstract” : “Zinc is one of the most abundant nutritionally essential elements in the human body. It is found in all body tissues with 85% of the whole body zinc in muscle and bone, 11% in the skin and the liver and the remaining in all the other tissues. In multicellular organisms, virtually all zinc is intracellular, 30-40% is located in the nucleus, 50% in the cytoplasm, organelles and specialized vesicles (for digestive enzymes or hormone storage) and the remainder in the cell membrane. Zinc intake ranges from 107 to 231 u03bcmol/d depending on the source, and human zinc requirement is estimated at 15 mg/d. Zinc has been shown to be essential to the structure and function of a large number of macromolecules and for over 300 enzymic reactions. It has both catalytic and structural roles in enzymes, while in zinc finger motifs, it provides a scaffold that organizes protein sub-domains for the interaction with either DNA or other proteins. It is critical for the function of a number of metalloproteins, inducing members of oxido-reductase, hydrolase ligase, lyase family and has co-activating functions with copper in superoxide dismutase or phospholipase C. The zinc ion (Zn++) does not participate in redox reactions, which makes it a stable ion in a biological medium whose potential is in constant flux. Zinc ions are hydrophilic and do not cross cell membranes by passive diffusion. In general, transport has been described as having both saturable and non-saturable components, depending on the Zn(II) concentrations involved. Zinc ions exist primarily in the form of complexes with proteins and nucleic acids and participate in all aspects of intermediary metabolism, transmission and regulation of the expression of genetic information, storage, synthesis and action of peptide hormones and structural maintenance of chromatin and biomembranes. u00a9 2003 Published by u00c9ditions scientifiques et mu00e9dicales Elsevier SAS.”, “author” : { “dropping-particle” : “”, “family” : “Tapiero”, “given” : “Haim”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tew”, “given” : “Kenneth D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Biomedicine and Pharmacotherapy”, “id” : “ITEM-1”, “issue” : “9”, “issued” : { “date-parts” : “2003” }, “page” : “399-411”, “title” : “Trace elements in human physiology and pathology: Zinc and metallothioneins”, “type” : “article-journal”, “volume” : “57” }, “uris” : “http://www.mendeley.com/documents/?uuid=a11de984-e447-4e07-a647-75da70590a1f” }, { “id” : “ITEM-2”, “itemData” : { “author” : { “dropping-particle” : “”, “family” : “Raimi, O.G., Falade, O. A., Folorunso, O. S. and Lawal”, “given” : “A. K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Department”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “id” : “ITEM-2”, “issue” : “2”, “issued” : { “date-parts” : “2012” }, “page” : “53-60”, “title” : “Zinc and iron levels in pregnancy : A review”, “type” : “article-journal”, “volume” : “22” }, “uris” : “http://www.mendeley.com/documents/?uuid=c1914ab0-d4c5-4cb8-9852-7c5798933139” } , “mendeley” : { “formattedCitation” : “(Raimi, O.G., Falade, O. A., Folorunso, O. S. and Lawal & Department, 2012; Tapiero & Tew, 2003)”, “plainTextFormattedCitation” : “(Raimi, O.G., Falade, O. A., Folorunso, O. S. and Lawal & Department, 2012; Tapiero & Tew, 2003)”, “previouslyFormattedCitation” : “(Raimi, O.G., Falade, O. A., Folorunso, O. S. and Lawal & Department, 2012; Tapiero & Tew, 2003)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Raimi, O.G., Falade, O. A., Folorunso, O. S. and Lawal & Department, 2012; Tapiero & Tew, 2003). Copper is mostly concentrated at areas in the body where metabolic activities are carried out such as kidneys, livers, heart and brain.

Figure 10: Diagram shows the effect of too much zinc and effect of being zinc deficient at different parts of the body ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.3390/ijerph7041342”, “ISBN” : “1660-4601”, “ISSN” : “16604601”, “PMID” : “20617034”, “abstract” : “Compared to several other metal ions with similar chemical properties, zinc is relatively harmless. Only exposure to high doses has toxic effects, making acute zinc intoxication a rare event. In addition to acute intoxication, long-term, high-dose zinc supplementation interferes with the uptake of copper. Hence, many of its toxic effects are in fact due to copper deficiency. While systemic homeostasis and efficient regulatory mechanisms on the cellular level generally prevent the uptake of cytotoxic doses of exogenous zinc, endogenous zinc plays a significant role in cytotoxic events in single cells. Here, zinc influences apoptosis by acting on several molecular regulators of programmed cell death, including caspases and proteins from the Bcl and Bax families. One organ where zinc is prominently involved in cell death is the brain, and cytotoxicity in consequence of ischemia or trauma involves the accumulation of free zinc. Rather than being a toxic metal ion, zinc is an essential trace element. Whereas intoxication by excessive exposure is rare, zinc deficiency is widespread and has a detrimental impact on growth, neuronal development, and immunity, and in severe cases its consequences are lethal. Zinc deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication.”, “author” : { “dropping-particle” : “”, “family” : “Plum”, “given” : “Laura M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rink”, “given” : “Lothar”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hajo”, “given” : “Haase”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Environmental Research and Public Health”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2010” }, “page” : “1342-1365”, “title” : “The essential toxin: Impact of zinc on human health”, “type” : “article-journal”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=f4d7d615-4621-40fd-95d3-73703581063e” } , “mendeley” : { “formattedCitation” : “(Plum et al., 2010)”, “plainTextFormattedCitation” : “(Plum et al., 2010)”, “previouslyFormattedCitation” : “(Plum et al., 2010)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Plum et al., 2010).

Zinc excess also affect human’s immune system. It causes the immune function to work more than it is supposed to especially mitogenic response and macrophages or T-lymphocyte functions. In adults, it will lead to deterioration of lymphocyte proliferative responses and a reduction in chemotaxis and phagocytosis of circulating polymorphonuclear leukocytes, ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/sj.ejcn.1601479”, “ISBN” : “0954-3007 (Print)\r0954-3007 (Linking)”, “ISSN” : “14765640”, “PMID” : “12142956”, “abstract” : “It is well recognized that zinc is an essential trace element, influencing growth and affecting the development and integrity of the immune system. Research has begun to clarify the molecular mechanisms underlying the action of zinc on the immune function. It is clear that this trace element has a broad impact on key immunity mediators, such as enzymes, thymic peptides and cytokines, explaining the paramount importance of zinc’s status on the regulation of lymphoid cell activation, proliferation and apoptosis. Ongoing and future studies regarding the immunological status of zinc deficiency ‘at risk’ groups could lead to public health interventions with nutritional doses of zinc supplements to prevent alteration of the immune system and improve resistance to infections.”, “author” : { “dropping-particle” : “”, “family” : “Dardenne”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “European Journal of Clinical Nutrition”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2002” }, “page” : “S20-S23”, “title” : “Zinc and immune function”, “type” : “article-journal”, “volume” : “56” }, “uris” : “http://www.mendeley.com/documents/?uuid=6c7c04b3-d85a-4605-837c-816aaf91bbfa” } , “mendeley” : { “formattedCitation” : “(Dardenne, 2002)”, “plainTextFormattedCitation” : “(Dardenne, 2002)”, “previouslyFormattedCitation” : “(Dardenne, 2002)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Dardenne, 2002). In children on the other hand, it will end up inducing anaemia, growth retardation and copper deficiency.
Symptoms of excess zinc which is between 50 to 150 milligrams in the body are as follows: nausea, vomiting, diarrhoea, abdominal cramps, loss of appetite and headaches. More severe bio-markers include shortness of breath, yellow skin, dizziness and chest pain (Bruso,J, 2018)
Conclusion
As we mentioned earlier, we did a review on the trace element, zinc as our research project. It is believed that zinc is the second highest component present in our body after iron. It plays an important role in the human body as it is needed for biological roles, the catalytic, the structural and the regulatory action. From our understanding, zinc binds with some of enzymes out of 300 types of enzymes present in our body. Zinc does not only focus on the growth of our health but also focuses on the well- being of our biological system. It is crucial for the structure and function of various proteins such as metallothein, MTs for zinc homeostasis and plays important role for human bodily processes from its involvement in function of the immune system, male and female reproductive system and in organ of human body like skin and brain. in addition, Alzheimer’s disease and cancer are correlated with the excess or deficiency of zinc. However. It can be a problem if our body have an excess accumulation of zinc or lack amount of zinc. It must be balance in concentration of zinc which is suitable for each part of body to be a healthy person. Many have used zinc supplementation for treatment of various disease related to zinc deficiency.
References
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