Arsenic Induced Oxidative Stress and Its Possible Reversal by Chelation Therapy

Abstract

Arsenic (As) is a metalloid listed in group Va of the periodic chart. It exists in nature in the oxidation states +V (arsenate), +III (arsenite), 0 (arsenic) and −III (arsine). In the aqueous environment inorganic arsenic appears commonly in the oxidation states +V and +III as arsenous acid (As (III)), arsenic acid (As (V)), and their salts. Chronic and acute exposures of arsenic leads to cancer, cardiovascular disease (hypertension and atherosclerosis), neurological disorders, gastrointestinal disturbances, liver disease and renal disease, reproductive health effects, dermal changes and other health disorders and also affects the antioxidant system in the body. Furthermore, reactive oxygen species (ROS)-mediated oxidative damage is a common denominator in arsenic pathogenesis. Formation of free radical such as superoxide radical due to cascade mechanism, combined with glutathione-depleting agents, increases the sensitivity of cells to arsenic toxicity. Formation of ROS/RNS, including peroxyl radicals (ROO^•), the superoxide radical, singlet oxygen, hydroxyl radical (OH^•) via the Fenton reaction, hydrogen peroxide, the dimethylarsenic radical, the dimethylarsenic peroxyl radical and/or oxidant-induced DNA damage, when both humans and animals are exposed to arsenic. In addition, arsenic induces the formation of oxidized lipids which in turn generate several bioactive molecules (ROS, peroxides and isoprostanes), of which aldehydes [malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE)] are the major end products. Various traditional antidotes are recommended for the present study such as DMSA (meso-2,3-dimercaptosuccinic acid), DMPS(2,3-dimercapto-1-propanesulfonic acid) DMPA (N-(2,3-dimercaptopropyl)-phthalamidic acid) BAL (2,3-dimercapto-1-propanol), Taurine (2-aminoethaesulfonic acid) against arsenic-induced toxicity. Recently, such phyto-antidotes like silibinin, arjunolic acid, vitamin C (ascorbic acid), vitamin E (α-tocopherol) and curcumin have played a major role in arsenic toxicity. Glutathione and antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase showed the protective role against arsenic-induced oxidative stress.