Advances in metal-induced oxidative stress and human disease

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.

https://www.mdpi.com/1660-4601/7/4/1342/pdf

The Essential Toxin: Impact of Zinc on Human Health

Publisher Summary This chapter discusses separate pools of CNS zinc, which are, vesicular zinc, free zinc, and protein-bound zinc Vesicular zinc is the one which is sequestered in the presynaptic vesicles of a special class of neurons, the zinc-containing neurons, which are found primarily in limbic, cerebrocortical, and corticofugal systems This vesicular zinc can be selectively stained by several histochemical procedures and is, therefore, accessible to histological and histoanalytical studies The second pool, free zinc, is an entirely hypothetical pool of ionic Zn +2 in the cytosol or interstitial fluid that may or may not be present in normal, healthy brain tissue The third pool of zinc is that which is bound firmly into the structure of the many zinc-containing enzymes in the brain The enzymatic zinc is, therefore, a stable pool, involved only in the specific function of the zinc-containing enzymes Zinc metalloenzymes are essential to the normal biology of brain cells, and any experimental treatment that is extreme enough to affect the metalloenzymes, such as prolonged zinc undernutrition or administration of chelators, can disrupt brain function through metalloenzymatic effects

Neurobiology of zinc and zinc-containing neurons.

The objective of this paper is to provide a current overview of the significance of zinc in human nutrition. To achieve this, the following issues are addressed: (1) the biochemistry and biology of zinc in the context of their relevance to zinc in human nutrition and to our understanding of the complexity and practical importance of human zinc deficiency; (2) the history of our understanding of human zinc deficiency with an emphasis both on its brevity and on notable recent progress; (3) the clinical spectrum of severe zinc deficiency; (4) the lack of ideal biomarkers for milder zinc deficiency states, with the consequent dependence on randomized, placebo-controlled intervention studies to ascertain their prevalence and clinical consequences, including growth delay, diarrhea, pneumonia, other infections, disturbed neuropsychological performance and abnormalities of fetal development; (5) the public health significance of human zinc deficiency in the developing world; (6) reasons for concern and unanswered questions about zinc nutriture in the United States; (7) the need for better understanding of human zinc metabolism and homeostasis (including its limitations) at a molecular, cellular, organ-system and whole body level and of factors that affect zinc bioavailability; and (8) potential strategies for the prevention and management of human zinc deficiency. This review concludes with an emphasis on the immediate need for expanded research in directions that have become increasingly well demarcated and impelling as a result of recent progress, which is summarized in this overview.

/pdf/human-zinc-deficiency-2bl1s7inwt.pdf

Human zinc deficiency.

Zinc is involved in a variety of biological processes, as a structural, catalytic, and intracellular and intercellular signaling component. Thus zinc homeostasis is tightly controlled at the whole ...

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism.

Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia.

SUMMARY A syndrome occurring in males, characterized by severe irondeficiency anemia, hypogonadism, dwarfism, hepatosplenomegaly, and geophagia, has been observed in villagers in Iran suffering from malnutrition. Eleven such patients, studied in detail, are described. Despite hepatosplenomegaly, results of the liver function tests were uniformly normal except for the serum alkaline phosphatase, which was consistently elevated. The anemia was not associated with blood loss, hookworm infestation, or intestinal malabsorption, and patients responded promptly to oral iron therapy. Although the diet contained adequate amounts of iron, it is believed that the predominantly wheat diet, with its high phosphate content, interfered with absorption because of the formation of insoluble iron complexes. Correction of the anemia resulted in marked decrease in the size of the liver and spleen. Prolonged follow-up of patients receiving a well balanced diet indicates that the endocrine abnormalities of growth and sexual development are reversible. The relationship of geophagia (which occurred in nearly all patients) to this syndrome is not clear and is discussed. The possibility of zinc deficiency is considered as an explanation of hypogonadism, dwarfism, and changes in alkaline phosphatase.

Syndrome of Iron Deficiency Anemia, Hepatosplenomegaly, Hypogonadism, Dwarfism and Geophagia

THE PURPOSE of this report is to present findings relating to gastrointestinal function in 11 adult patients with severe and prolonged iron deficiency who were studied in Iran in 1960. Little information is available on intestinal function in iron deficiency. Furthermore, these patients had no blood loss. Iron-deficiency anemia in the absence of blood loss is excessively rare in the United States. Thus, our finding of this as a fairly common condition in Iran merits attention. Until recent years, the relationship of the gastrointestinal tract to iron-deficiency anemia has been studied almost entirely in respect to gastric acidity. Faber 1 noted decreased gastric acidity in hypochromic anemia in 1913. Others have confirmed this observation, but it is generally believed that achlorhydria is the result rather than an etiological factor in iron-deficiency anemia. However, this question is still debatable. 2-4 With the advent of more precise laboratory procedures for measurement

Gastrointestinal function in iron-deficiency anemia.

A syndrome occurring in males, characterized by severe iron deficiency anemia, hypogonadism, dwarfism, hepatosplenomegaly and geophagia, has been observed in villagers in Iran suffering from malnutrition. Eleven such patients, studied in detail, are described. Despite hepatosplenomegaly, results of the liver function tests were uniformly normal except for the serum alkaline phosphatase, which was consistently elevated. The anemia was not associated with blood loss, hookworm infestation or intestinal malabsorption, and responded promptly to oral iron therapy. Although the diet contained adequate amounts of iron it is believed that the predominantly wheat diet, with its high phosphate content, interfered with absorption because of the formation of insoluble iron complexes. Correction of the anemia resulted in marked decrease in the size of the liver and spleen. Prolonged follow-up of patients receiving a well balanced diet indicates that the endocrine abnormalities of growth and sexual development are reversible. The relationship of geophagia (which occurred in nearly all patients) to this syndrome is not clear, and is discussed. The possibility of zinc deficiency is considered as an explanation of hypogonadism, dwarfism and changes in alkaline phosphatase.

Manucher Nadimi

Papers

Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia.

Syndrome of Iron Deficiency Anemia, Hepatosplenomegaly, Hypogonadism, Dwarfism and Geophagia

Gastrointestinal function in iron-deficiency anemia.

Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia