Effects of exogenous glutathione on arsenic distribution and NO metabolism in brain of female mice exposed to sodium arsenite through drinking water.

Objective To explore the effects of exogenous glutathione on arsenic distribution and nitric oxide (NO) metabolism in the brain of mice exposed to arsenite through drinking water. Methods Female Kunming mice were randomly divided into 5 groups, eight in each, and the mice were exposed to sodium arsenite through drinking water at doses of 0 mg/L (control) and 50 mg/L arsenic for 4 consecutive weeks, on the fourth week, with the exposure of arsenic, glutathione was given through intraperitoneal injection at doses of 200 mg/kg b.w, 400 mg/kg b.w or 800 mg/kg b.w, respectively for 7 days. In the end of treatment, the samples of blood and brain were collected. Levels of inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethylarsenic acid (DMA) were determined by HG-AAS method. Activities of nitric oxide synthase (NOS) and the concentrations of NO were determined with kits. Results Compared with those in single arsenic group, glutathione significantly decreased levels of iAs, MMA and total arsenic levels (TAs) in the blood and levels of DMA and TAs in the brain. Activities of NOS and levels of NO in As group were significantly lower than those in control, however administration of glutathione could ameliorate these toxic effects, and NOS activities in groups treated with 400 mg/kg b.w and 800 mg/kg b.w glutathione were significantly higher than those in single arsenic group. Conclusion Exogenous glutathione may promote methylation of arsenic, therefore reduce arsenic levels in both blood and brain. Moreover, it is proposed that administration of exogenous glutathione can ameliorate the adverse effects of arsenic on NO metabolism in the brain via decreasing the brain arsenic burden.