Effects of glutathione on the in vivo metabolism and oxidative stress of arsenic in mice.

Abstract

In this study, we investigated the in vivo effects of exogenous glutathione and buthionine sulfoximine on arsenic methylation and antioxidant capacity in mice exposed to arsenic via drinking water. Thirty-six female albino mice were randomly divided into six groups. All groups were given free access to drinking water that contained arsenic continuously except the control group. After ten days, mice were treated with different levels of glutathione or buthionine sulfoximine. The levels of the metabolites of arsenic were determined in the liver and urine. The levels of glutathione and total antioxidant capacity were determined in the whole blood and liver. Our results showed that the increase of arsenic species in the liver as well as the decrease of blood and hepatic glutathione and total antioxidant capacity, were all relieved by exogenous glutathione consistently. We also observed the involvement of glutathione in promoting arsenic methylation and urinary elimination in vivo. Increase of total arsenic in the urine was mainly due to the increase of dimethylated arsenic. Furthermore, administration of glutathione increased the first methylation ratio and secondary methylation ratio in the liver and urine, which resulted in the consequent increase of dimethylated arsenic percent and decrease of inorganic arsenic percent in the urine. Opposite effects appeared with the administration of buthionine sulfoximine, a scavenger of glutathione. Our study indicated that exogenous glutathione not only accelerated the methylation and the excretion of arsenic, but also relieve the arsenic-induced oxidative stress. This provides a potential useful chemopreventive dietary component for human populations being at risk of arsenic exposure.