Oxidation and detoxification of trivalent arsenic species

• Published in: Toxicology and applied pharmacology Vol. 193; no. 1; pp. 1 - 8
• Main Authors: Aposhian, H.Vasken, Zakharyan, Robert A., Avram, Mihaela D., Kopplin, Michael J., Wollenberg, Michael L.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15-11-2003; Elsevier
• Subjects: Allopurinol - pharmacology; Animals; Arsenates - chemistry; Arsenates - metabolism; Arsenates - toxicity; Arsenicals - chemistry; Arsenicals - metabolism; Arsenites - chemistry; Arsenites - metabolism; Arsenites - toxicity; Biological and medical sciences; Cacodylic Acid - chemistry; Cacodylic Acid - metabolism; Cacodylic Acid - toxicity; Catalase - pharmacology; Cattle; Chemical and industrial products toxicology. Toxic occupational diseases; Enzyme Inhibitors - pharmacology; Hydrogen Peroxide - chemistry; Hydrogen Peroxide - metabolism; Hypoxanthine - metabolism; Medical sciences; Metals and various inorganic compounds; Organometallic Compounds - chemistry; Organometallic Compounds - metabolism; Organometallic Compounds - toxicity; Oxidation-Reduction; Toxicology; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - metabolism; Arsenic V; Toxicity; Detoxification; Metabolism toxicity relation; Arsenic III; Metabolism; In vitro; Comparative study
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/S0041-008X(03)00324-7

Arsenic compounds with a +3 oxidation state are more toxic than analogous compounds with a +5 oxidation state, for example, arsenite versus arsenate, monomethylarsonous acid (MMA
III) versus monomethylarsonic acid (MMA
V), and dimethylarsinous acid (DMA
III) versus dimethylarsinic acid (DMA
V). It is no longer believed that the methylation of arsenite is the beginning of a methylation-mediated detoxication pathway. The oxidation of these +3 compounds to their less toxic +5 analogs by hydrogen peroxide needs investigation and consideration as a potential mechanism for detoxification. Xanthine oxidase uses oxygen to oxidize hypoxanthine to xanthine to uric acid. Hydrogen peroxide and reactive oxygen are also products. The oxidation of +3 arsenicals by the hydrogen peroxide produced in the xanthine oxidase reaction was blocked by catalase or allopurinol but not by scavengers of the hydroxy radical, e.g., mannitol or potassium iodide. Melatonin, the singlet oxygen radical scavenger, did not inhibit the oxidation. The production of H
2O
2 by xanthine oxidase may be an important route for decreasing the toxicity of trivalent arsenic species by oxidizing them to their less toxic pentavalent analogs. In addition, there are many other reactions that produce hydrogen peroxide in the cell. Although chemists have used hydrogen peroxide for the oxidation of arsenite to arsenate to purify water, we are not aware of any published account of its potential importance in the detoxification of trivalent arsenicals in biological systems. At present, this oxidation of the +3 oxidation state arsenicals is based on evidence from in vitro experiments. In vivo experiments are needed to substantiate the role and importance of H
2O
2 in arsenic detoxication in mammals.