Selenium, an antioxidant, attenuates methamphetamine-induced dopaminergic toxicity and peroxynitrite generation
Selenium, an antioxidant, attenuates methamphetamine-induced dopaminergic toxicity and peroxynitrite generation
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DOI：
10.1016/s0006-8993(99)02249-0
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发表时间：
2000-02-07
期刊：
影响因子：
2.9
通讯作者：
Ali, SF
中科院分区：
文献类型：
--
作者：
Imam, SZ;Ali, SF
已知甲基苯丙胺(METH)通过产生活性氧和氮物种而产生神经毒性。据报道，抗氧化剂硒对冰毒引起的小鼠尾状核多巴胺能神经毒性有保护作用。本文研究了补硒对冰毒诱导的过氧亚硝酸根生成的体内外效应。将培养的PC12细胞暴露于200亩M冰毒中，加或不加10亩M和20亩M硒(冰毒暴露前30分钟)。染毒24 h后，PC12细胞中多巴胺及其代谢物DOPAC和HVA显著减少，过氧亚硝酸根的标志物3-硝基酪氨酸(3-NT)显著生成。补硒可减轻PC12细胞多巴胺及其代谢产物DOPAC和HVA的耗竭和3-NT的形成。在体内实验中，成年雄性小鼠在多次注射冰毒(4×10 mg/kg)前1周和注射后1周分别在饮用水中补充硒。间隔2小时)或等量的生理盐水。补充Se可减少冰毒处理所致纹状体内3-NT的形成。这些数据表明冰毒所致的神经毒性是由过氧亚硝酸盐的产生所介导的，而硒在冰毒所致的神经毒性中起保护作用。(C)2000由爱思唯尔科学公司出版。保留所有权利。
Methamphetamine (METH) has been known to produce neurotoxicity via generation of reactive oxygen and nitrogen species. Selenium, an antioxidant, was reported to protect against METH-induced dopaminergic neurotoxicity in mouse caudate nucleus. In the present study, the in vitro and in vivo efficacy of the supplementation of selenium was studied in METH-induced generation of peroxynitrite. PC12 cell cultures were exposed to 200 mu M METH either with or without 10 mu M and 20 mu M selenium (30 min prior to METH exposure). After 24 h, METH exposure resulted in the significant depletion of dopamine, and its metabolites DOPAC and HVA, as well as the significant formation of 3-nitrotyrosine (3-NT), a marker of peroxynitrite generation, in PC12 cell cultures. Selenium supplementation attenuated the depletion of dopamine and its metabolites, DOPAC and HVA and the formation of 3-NT in PC12 cells. For in vivo studies, adult male mice were supplemented with selenium in drinking water, 1 week before and 1 week after the multiple injections of METH (4 X 10 mg/kg, i.p. at 2-h interval) or an equivalent volume of saline. The supplementation of Se attenuated the formation of 3-NT in the striatum resulting from METH treatment. These data suggest that METH-induced neurotoxicity is mediated by the production of peroxynitrite, and selenium plays a protective role in METH-induced neurotoxicity. (C) 2000 Published by Elsevier Science B.V. All rights reserved.