Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease

Wayne State University School of Medicine, Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI.
Advances in Nutrition (Impact Factor: 4.71). 03/2013; 4(2):176-190. DOI: 10.3945/an.112.003210
Source: PubMed


The essentiality of zinc in humans was established in 1963. During the past 50 y, tremendous advances in both clinical and basic sciences of zinc metabolism in humans have been observed. The major factor contributing to zinc deficiency is high phytate-containing cereal protein intake in the developing world, and nearly 2 billion subjects may be zinc deficient. Conditioned deficiency of zinc has been observed in patients with malabsorption syndrome, liver disease, chronic renal disease, sickle cell disease, and other chronic illnesses. Major clinical problems resulting from zinc deficiency in humans include growth retardation; cell-mediated immune dysfunction, and cognitive impairment. In the Middle East, zinc-deficient dwarfs did not live beyond the age of 25 y, and they died because of intercurrent infections. In 1963, we knew of only 3 enzymes that required zinc for their activities, but now we know of >300 enzymes and >1000 transcription factors that are known to require zinc for their activities. Zinc is a second messenger of immune cells, and intracellular free zinc in these cells participate in signaling events. Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson's disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti-inflammatory agent.

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    • "Zinc evoked a concentrationdependent increase in the viability of the cells at lower range and decrease in the viability at higher range. At lower range of concentration cell were able to grow at higher rates [23] [24] [25]. Apart from this normal cell survived highest concentration of Zinc supplementation i.e. 80 µM, than that of cancer cells. "
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    ABSTRACT: — Zinc is the most abundant trace element which has role in genetic stability and function, present in the cell nucleus, nucleolus and chromosomes, and stabilizes the structure of DNA, RNA and ribosomes and found in many Zinc binding proteins. The purpose of this study is to access the Zinc cytotoxicity, total cellular Zinc content and total Zinquin Acid (Fluorophore) interaction with cellular Zinc in response to six different Zinc gradient medium using MTT assay, Atomic absorption spectroscopy and Fluorescence spectroscopy respectively. Statistical analysis one way ANOVA and Tukey HSD test for mean comparison was performed. Our findings are, significant differences on normal cell line survival of 108.7% at 10 µM supplemented medium was seen. Cytotoxicity was seen at 80 µM of 89.78% and 86.46% in MDA-MB-231 and U-87-MG Cell lines respectively. Significant increase in cellular influx and accumulation of Zn2+ ions was observed in all cell lines. Fluorescence intensity emission peak response increased with supplementation of gradient medium, which supported the hypothesis of increased cellular Zinc accumulation, λ-max shifting to shorter wavelength i.e. idea supports blue shift emission of Zinquin Acid which interacts not only with free labile Zinc ions but with Zinc bound proteins. Zinc based fluorescence probes help detection of altered expression of Zinc.
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    • "Limited maternal dietary selenium also restricts transmission to the neonate that has been reported to result in impaired in vitro activation of thymocytes, and decreased proportions of circulating adaptive immune cells in the neonate (117). Zinc deficiency has been associated with impaired growth and immune cell functions (118) and reprograming of the immune system from adaptive to more innate immune responses (119). Randomized controlled trials of zinc supplementation in small for gestational age term infants have resulted in decreases in diarrhea, pneumonia infection, and may reduce overall mortality in some settings (120). "
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    ABSTRACT: The concept of immunological memory stipulates that past exposures shape present immune function. These exposures include not only specific antigens impacting adaptive immune memory but also conserved pathogen or danger associated molecular patterns that mold innate immune responses for prolonged periods of time. It should thus not come as a surprise that there is a vast range of external or environmental factors that impact immunity. The importance of environmental factors modulating immunity is most readily recognized in early life, a period of rapidly changing environments. We here summarize available data on the role of environment shaping immune development and from it derive an overarching hypothesis relating the underlying molecular mechanisms and evolutionary principles involved.
    Frontiers in Immunology 09/2014; 5:434. DOI:10.3389/fimmu.2014.00434
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    • "Approximately 10% of all proteins bind with Zn which regulates their biological activity (Fukada et al., 2011). Zn deficiency is an emerging dietary disorder whereas decreased concentrations of this metal in serum have recently been associated with preeclampsia (Prasad, 2013; Sarwar et al., 2013). It was also found that Zn content in endometrial tissue can undergo cyclic variations reaching maximum concentrations in the late secretory phase and minimal levels during the late proliferative phase which potentially underlines its specific role in the menstrual cycle (Hagenfeldt et al., 1973). "
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    ABSTRACT: Human endometrium is a thick, blood vessel-rich, glandular tissue which undergoes cyclic changes and is potentially sensitive to the various endogenous and exogenous compounds supplied via the hematogenous route. As recently indicated, several metals including Cd, Pb, Cr and Ni represent an emerging class of potential metalloestrogens and can be implicated in alterations of the female reproductive system including endometriosis and cancer. In the present study, we investigated the content of five metals: Cd, Cr, Ni, Pb and Zn in 25 samples of human endometrium collected from Polish females undergoing diagnostic or therapeutic curettage of the uterine cavity. The overall mean metal concentration analyzed using microwave induced plasma atomic emission spectrometry MIP-OES) decreased in the following order: Cr>Pb>Zn>Ni>Cd. For the first time it was demonstrated that cigarette smoking significantly increases the endometrial content of Cd and Pb. Concentration of these metals was also positively correlated with years of smoking and the number of smoked cigarettes. Tissue samples with recognized histologic lesions (simple hyperplasia, polyposis and atrophy) were characterized by a 2-fold higher Cd level. No relation between the age of the women and metal content was found. Our study shows that human endometrium can be a potential target of metal accumulation within the human body. Quantitative analyses of endometrial metal content could serve as an additional indicator of potential impairments of the menstrual cycle and fertility.
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