Glutathione and methylation of inorganic arsenic in hamsters

AbstractThe effect of giutathione (GSH) concentrations in livers and kidneys of hamsters on the toxicity and methylation of arsenite in these animals was studied. No significant changes in hepatic and renal GSH concentrations were observed after a single arsenite administration (5 mg As kg−1, p.o.). When buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, was given (4 mmol kg−1, i.p.) two hours before administration of arsenite, hepatic and renal GSH concentrations were more severely and persistently depressed than in the case of BSO administration not followed by arsenite. Hamsters treated with BSO plus arsenite suffered from severe nephrotoxicity (acute renal failure) characterized by increases in plasma creatinine and urea nitrogen and by proximal tubular necrosis. Concurrently, transient hepatotoxicity was observed in the BSO plus arsenite group. Neither arsenite alone nor BSO alone produced liver or kidney injury. The BSO plus arsenite‐treated animals excreted in the urine only 3.5% of the arsenic dose during the 72 h period after administration of arsenite, probably because of a decrease in urine volume caused by kidney injury, whereas the arsenite‐only group excreted 27%. In addition, BSO pretreatment influenced the relative proportion of arsenic metabolites excreted in the urine during the first 24 h after administration. Urinary metabolites in the BSO plus arsenite group were predominantly inorganic arsenic. These results suggest that GSH provides protection against arsenic toxicity.