Zinc Toxicity in Humans

In dealing with zinc’s essentiality/toxicity (Dr. Jekyll and Mr. Hyde) duality, biological systems have developed the homeostatic ability to tightly regulate the zinc levels through a complicated framework for import and export, transport and distribution and sensing of zinc status to ensure that zinc does not participate in toxic reactions. In spite of the thousands of papers that have been published on biological effects of zinc, the challenge of quantifying the range of exposure doses that constitute zinc deficiency versus excess remains unresolved. Recent studies with better design and more sensitive methods point to a considerable overlap between what has generally been considered to be the essential dose and toxic dose, suggesting that the dose-response curve for zinc may not be a ‘‘U’’ but a ‘‘V’’. Although zinc is not involved in cellular redox cycle and has traditionally been regarded as relatively nontoxic, recent studies increasingly show that free ionic zinc (Zn2þ) is a potent killer of neurons, glia and other cell types. Zinc concentrations in the brain are maintained within a narrow range of 600-800 ng/L with deviations substantially above and below this range being proconvulsive and cytolethal respectively. Free zinc ion may be much more toxic biologically than is generally realized. The physiologically optimal Zn2þ concentration in eukaryotic cells is around 10 ng/L and when the zinc level falls below 0.06 ng/L apoptosis can be triggered but when the level rises above 60 ng/L toxicity can ensure. The evolution of biomolecules to scavenge the zinc ions was crucially important in ameliorating the cellular toxicity and facilitating the myriad cellular uses for zinc.