Mechanism for arsenic-induced toxic effects

The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed through food, water, air, and soil. It causes various biological effects on cells and tissues. The metabolism of arsenic has an important role in its toxicity. This metabolism involves methyltransferase mediated reduction to a trivalent state followed by oxidative methylation to a pentavalent state. The pentavalent arsenicals are reported to be less potent toxicants than the trivalent arsenicals including those that are methylated. Arsenic-induced toxicity is believed to be mediated via reactive oxygen species (ROS) generation, Ca2+ accumulation, caspase-3 up-regulation, Bcl-2 down-regulation, and p-53 deficiency. Alterations of these factors from normal physiology might play prominent roles in carcinogenicity, cardiovascular, testicular, genotoxicity, diabetes, and nervous systems disorders. The exact mechanisms in arsenic toxicity and its subsequent organ pathophysiology are not well defined to date. Potential mechanisms of various types of arsenic-induced cancer may include oxidative stress, co-carcinogenesis and tumor promotion, genotoxicity, altered DNA methylation, altered cell proliferation, etc. As a preventive and curative measure of arsenic toxicity, combination therapies using antioxidants (N-acetylcysteine, α-lipoic acid, quercetin, etc.) and a thiol-chelating agent (with a proper chelator) can be considered as a better therapeutic approach than chelation therapy alone. We intend to summarize the up-to-date knowledge from literature on the molecular and cellular mechanisms of arsenic toxicity and usefulness of antioxidants in preventing these alterations.