Effects of exogenous glutathione on arsenic burden and NO metabolism in brain of mice exposed to arsenite through drinking water.
Chronic exposure to inorganic arsenic (iAs) is associated with neurotoxicity. Studies to date have disclosed that methylation of ingested iAs is the main metabolic pathway, and it is a process relying on reduced glutathione (GSH). The aim of this study was to explore the effects of exogenous GSH on arsenic burden and metabolism of nitric oxide (NO) in the brain of mice exposed to arsenite via drinking water. Mice were exposed to sodium arsenite through drinking water contaminated with 50 mg/L arsenic for 4 weeks and treated intraperitoneally with saline solution, 200 mg/kg body weight (b.w), 400 mg/kg b.w, or 800 mg/kg b.w GSH, respectively, at the 4th week. Levels of iAs, monomethylarsenic acid, and dimethylarsenic acid (DMAs) in the liver, blood, and brain were determined by method of hydride generation coupled with atomic absorption spectrophotometry. Activities of nitric oxide synthase (NOS) and contents of NO in the brain were determined by colorimetric method. Compared with mice exposed to arsenite alone, administration of GSH increased dose-dependently the primary and secondary methylation ratio in the liver, which caused the decrease in percent iAs and increase in percent DMAs in the liver, as a consequence, resulted in significant decrease in iAs levels in the blood and total arsenic levels in both blood and brain. NOS activities and NO levels in the brain of mice in iAs group were significantly lower than those in control; however, administration of GSH could increase significantly activities of NOS and contents of NO. Findings from this study suggested that exogenous GSH could promote both primary and secondary arsenic methylation capacity in the liver, which might facilitate excretion of arsenicals, and consequently reduce arsenic burden in both blood and brain and furthermore ameliorate the effects of arsenicals on NO metabolism in the brain.
Wang
Yan
Y
Department of Environmental and Occupational Health, School of Public Health, China Medical University, Heping District, Shenyang, Liaoning, People's Republic of China.
Zhao
Fenghong
F
Jin
Yaping
Y
Zhong
Yuan
Y
Yu
Xiaoyun
X
Li
Gexin
G
Lv
Xiuqiang
X
Sun
Guifan
G
D000818:Animals; D001151:Arsenic / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D018053:Arsenites / Q000378:metabolism / Q000633:toxicity*; D001921:Brain / Q000378:metabolism*; D002101:Cacodylic Acid / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008745:Methylation; D051379:Mice; D009589:Nitrogen Oxides / Q000378:metabolism*; D011897:Random Allocation; D013997:Time Factors; D014881:Water Supply
D018053:Arsenites; D009589:Nitrogen Oxides; D002101:Cacodylic Acid; D005978:Glutathione; D001151:Arsenic