Effects of exogenous glutathione on arsenic burden and NO metabolism in brain of mice exposed to arsenite through drinking water
Effects of exogenous glutathione on arsenic burden and NO metabolism in brain of mice exposed to arsenite through drinking water
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外源性谷胱甘肽对饮水亚砷酸盐小鼠脑内砷负荷及NO代谢的影响
DOI：
10.1007/s00204-010-0573-1
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发表时间：
2011-03
影响因子：
6.1
通讯作者：
Sun, Guifan
中科院分区：
文献类型：
--
作者：
Wang, Yan;Zhao, Fenghong;Jin, Yaping;Zhong, Yuan;Yu, Xiaoyun;Li, Gexin;Lv, Xiuqiang;Sun, Guifan
无机砷（iAs）的慢性暴露与神经毒性有关。迄今为止的研究表明，摄入的iAs的甲基化是主要的代谢途径，并且这是一个依赖于还原型谷胱甘肽（GSH）的过程。本研究旨在探讨外源性GSH对饮水砷暴露小鼠脑砷负荷及一氧化氮（NO）代谢的影响。通过饮用含砷量为50 mg/L的亚砷酸钠染毒小鼠4周，第4周分别腹腔注射GSH 200 mg/kg（B.w）、400 mg/kg B.w和800 mg/kg B.w。氢化物发生-原子吸收分光光度法测定肝脏、血液和脑中iAs、单甲基砷酸和二甲基砷酸（DMAs）的水平。比色法测定脑组织一氧化氮合酶（NOS）活性和一氧化氮（NO）含量。与单独砷暴露组相比，GSH剂量依赖性地增加了肝脏中初级和次级甲基化比率，导致肝脏中iAs百分比降低和DMAs百分比升高，从而导致血中iAs水平和血、脑中总砷水平显著降低。iAs组小鼠脑内NOS活性和NO含量均显著低于对照组;外源性GSH可促进肝脏中砷的初级和次级甲基化能力，从而促进砷的排泄，从而降低血砷和脑砷负荷，进而改善砷剂对脑NO代谢的影响。
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.
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影响因子：
10.4
作者：
Wasserman GA;Liu X;Parvez F;Ahsan H;Factor-Litvak P;Kline J;van Geen A;Slavkovich V;Loiacono NJ;Levy D;Cheng Z;Graziano JH
通讯作者：
Graziano JH
影响因子：
10.4
作者：
Wasserman GA;Liu X;Parvez F;Ahsan H;Levy D;Factor-Litvak P;Kline J;van Geen A;Slavkovich V;LoIacono NJ;Cheng Z;Zheng Y;Graziano JH
通讯作者：
Graziano JH
影响因子：
8.3
作者：
Calderón, J;Navarro, ME;Díaz-Barriga, F
通讯作者：
Díaz-Barriga, F
影响因子：
5.3
作者：
Hopper, Rachel A.;Garthwaite, John
通讯作者：
Garthwaite, John
影响因子：
4.4
作者：
S. Zarazúa;F. Pérez-Severiano;J. M. Delgado;Luz M Martínez;D. Ortiz-Pérez;M. Jiménez-Capdeville
通讯作者：
S. Zarazúa;F. Pérez-Severiano;J. M. Delgado;Luz M Martínez;D. Ortiz-Pérez;M. Jiménez-Capdeville