外源性谷胱甘肽对饮水砷暴露雌性小鼠脑砷形态及一氧化氮代谢的影响

目的 探讨外源性谷胱甘肽(glutathione,GSH)对饮水砷暴露小鼠脑中砷形态分布及一氧化氮(nitric oxide,NO)代谢的影响.方法 将40只雌性昆明小鼠随机分为对照组、单独染砷(NaAsO_2)组及低剂量(200mg/kg)、中剂量(400mg/kg)或高剂量(800mg/kg)GSH干预组,每组8只.染毒组小鼠饮水染砷4周,在最后一周,在染砷同时腹腔注射不同剂量GSH.末次注射后24h处死小鼠,取血和脑组织,分别检测无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)含量及脑中一氧化氮合酶(NOS)活力和NO含量.结果 GSH干预组小鼠血中iAs、MMA和总砷(TAs)含量及脑中DMA和TAs含量与单独染砷组比较显著下降.与对照组相比,单独染砷组小鼠脑中NOS活力及NO含量显著降低.与单独染砷组比较,中、高剂量GSH干预组小鼠脑中NOS活力显著升高.结论 给予外源性GSH可减少血液和脑组织中的砷负荷,进而改善砷对脑内NO代谢的影响.

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.Activimes of mice oxide symhase (NOS) a and the correcmi ations 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.