Metabolism and toxicity of arsenicals in mammals.

Arsenic (As) is a metalloid usually found in organic and inorganic forms with different oxidation states, while inorganic form (arsenite As-III and arsenate As-v) is considered to be more hazardous as compared to organic form (methylarsonate and dimethylarsinate), with mild or no toxicity in mammals. Due to an increasing trend to using arsenicals as growth promoters or for treatment purposes, the understanding of metabolism and toxicity of As gets vital importance. Its toxicity is mainly depends on oxi-reduction states (As-III or As-v) and the level of methylation during the metabolism process. Currently, the exact metabolic pathways of As have yet to be confirmed in humans and food producing animals. Oxidative methylation and glutathione conjugation is believed to be major pathways of As metabolism. Oxidative methylation is based on conversion of Arsenite in to mono-methylarsonic acid and di-methylarsenic acid in mammals. It has been confirmed that As is only methylated in the presence of glutathione or thiol compounds, suggesting that As is being methylated in trivalent states. Subsequently, non-conjugated trivalent arsenicals are highly reactive with thiol which converts the trivalent arsenicals in to less toxic pentavalent forms. The glutathione conjugate stability of As is the most important factor for determining the toxicity. It can lead to DNA damage by alerting enzyme profile and production of reactive oxygen and nitrogen species which causes the oxidative stress. Moreover, As causes immune-dysfunction by hindering cellular and humeral immune response. The present review discussed different metabolic pathways and toxic outcomes of arsenicals in mammals which will be helpful in health risk assessment and its impact on biological world.