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Abstract
Cadmium (Cd) is a well-known environmental toxicant posing significant health risks. In particular, Cd exposure is associated with numerous disorders including cancer, neurodegeneration, and metabolic syndrome. Despite the presence of multiple associated disorders, adverse health effects of the metal are mainly related to the universal mechanisms of toxicity that are tightly associated with Cd chemistry. Binding to sulfur- and nitrogen-containing functional groups, as well as the displacement of the essential element (zinc) from metalloenzymes, are considered as the primary mechanisms providing the basis for cadmium toxicity. Proinflammatory effect of Cd is associated with overproduction of proinflammatory cytokinestumor necrosis factor-α (TNF-α), interleukin (IL)-1, and IL-6) and a significant Cd-induced decrease in anti-inflammatory cytokine (IL-1 receptor antagonist, IL-4, IL-6, IL-10, IL-13) production. Proinflammatory activity of cadmium is tightly related to the induction of oxidative stress through various pathways. Cd is capable of replacement of iron and copper in various proteins resulting in increased free redox active metal pool and activation of Fenton chemistry. In turn, inhibition of the electron transport chain is associated with impaired oxygen handling and increased rate of reactive oxygen species production. Cd-induced inhibition of antioxidant enzymes aggravates free radical damage to macromolecules, including nucleic acids. The latter results in genotoxic effects of cadmium and subsequent altered gene regulation. Therefore, modulation of the mechanisms of Cd toxicity may be a useful measure for prevention of adverse health effects of Cd exposure.
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