Effects of exogenous methionine on arsenic burden and NO metabolism in brain of mice exposed to arsenite through drinking water
Effects of exogenous methionine on arsenic burden and NO metabolism in brain of mice exposed to arsenite through drinking water
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DOI：
10.1002/tox.20689
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发表时间：
2012-12
影响因子：
4.5
通讯作者：
Fenghong Zhao;Yan Wang;Yaping Jin;Y. Zhong;Xiaoyun Yu;Gexin Li;Xiuqiang Lv;Guifan Sun
中科院分区：
文献类型：
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作者：
Fenghong Zhao;Yan Wang;Yaping Jin;Y. Zhong;Xiaoyun Yu;Gexin Li;Xiuqiang Lv;Guifan Sun
本研究旨在探讨外源性蛋氨酸（Met）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周分别腹腔注射生理盐水、100 mg/kg体重（B.w）、200 mg/kg B.w和400 mg/kg B.w的蛋氨酸。采用氢化物发生-原子吸收分光光度法测定肝脏、血液和脑中无机砷（iAs）、一甲基砷酸（MMAs）和二甲基砷酸（DMAs）的含量。比色法测定脑组织一氧化氮合酶（NOS）活性和NO含量。与单独染毒组相比，染毒组小鼠肝脏一级甲基化率显著升高，导致肝脏中iAs含量降低，DMAs含量升高，血中iAs、MMAs、总砷含量降低，脑中DMAs、总砷含量降低。单独染毒组小鼠脑组织NOS活性和NO含量均显著低于对照组，而蛋氨酸染毒组小鼠脑组织NO含量显著高于对照组。本研究结果提示，外源性蛋氨酸可促进肝脏中砷的初级甲基化，从而增加甲基化砷的产生，促进砷的排泄。因此，砷负荷在血液和脑中的降低，并在脑中的NO代谢的毒性作用得到改善。© 2011 Wiley Periodicals，Inc.环境毒理学，2012年。
The aim of this study was to explore the effects of exogenous methionine (Met) 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 four consecutive weeks, and treated intraperitoneally with saline solution, 100 mg/kg body weight (b.w), 200 mg/kg b.w or 400 mg/kg b.w of Met, respectively at the fourth week. Levels of inorganic arsenic (iAs), monomethylarsenic acid (MMAs), and dimethylarsenic acid (DMAs) in the liver, blood and brain were determined by method of hydride generation coupled with atomic absorption spectrophotometry. Nitric oxide synthase (NOS) activities and NO levels in the brain were determined by colorimetric method. Compared with mice exposed to arsenite alone, administration of Met increased significantly the primary methylation ratio in the liver, which resulted in decrease of percent iAs and increase of percent DMAs in the liver, and decrease of iAs, MMAs and total arsenic levels (TAs) in the blood and DMAs and TAs in the brain. NOS activities and NO levels in the brain of mice exposed to arsenite alone were significantly lower than those in control, however administration of Met could increase significantly NO levels. Findings from this study suggested that exogenous Met could benefit the primary arsenic methylation in the liver, which might increase the production of methylated arsenicals and facilitate arsenic excretion. As a consequence, arsenic burden in both blood and brain was reduced, and toxic effects on NO metabolism in the brain were ameliorated. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2012.