Methamphetamine generates peroxynitrite and produces dopaminergic neurotoxicity in mice: protective effects of peroxynitrite decomposition catalyst
Methamphetamine generates peroxynitrite and produces dopaminergic neurotoxicity in mice: protective effects of peroxynitrite decomposition catalyst
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DOI：
10.1016/s0006-8993(99)01663-7
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发表时间：
1999-08-07
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;Crow, JP;Ali, SF
甲基苯丙胺（METH）诱导的多巴胺能神经毒性被认为是由氧化应激和自由基产生产生。本研究进行调查，如果甲基产生过氧亚硝酸盐和产生多巴胺能神经毒性。我们还研究了这种过氧亚硝酸根的产生是否可以被选择性过氧亚硝酸根分解催化剂5，10，15，20-四（N-甲基-4 '-吡啶基）卟啉合铁III（FeTMPyP）阻断，并防止MET诱导的多巴胺能神经毒性。METH的给药导致纹状体中3-硝基酪氨酸（3-NT）（过氧亚硝酸盐生成的体内标记物）的显著形成，并导致体温显著升高。与对照组相比，METH注射还导致纹状体中多巴胺（DA）、3，4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）的浓度分别显著降低76%、53%和40%。与METH组相比，用FeTMPyP治疗阻断了66%的3-NT形成。FeTMPyP处理还提供了针对MET诱导的体温过高和DA、DOPAC和HVA消耗的显著保护。单独施用FeTMPyP既不导致3-NT形成，也对DA或其代谢物浓度没有任何显著影响。这些研究结果表明，过氧亚硝酸盐在甲基苯丙胺诱导的多巴胺能神经毒性中起作用，也表明过氧亚硝酸盐分解催化剂可能有利于精神兴奋剂滥用的管理。(C)1999年由Elsevier Science B. V.出版，版权所有。
Methamphetamine (METH)-induced dopaminergic neurotoxicity is believed to be produced by oxidative stress and free radical generation. The present study was undertaken to investigate if METH generates peroxynitrite and produces dopaminergic neurotoxicity. We also investigated if this generation of peroxynitrite can; be blocked by a selective peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and protect against METH-induced dopaminergic neurotoxicity. Administration of METH resulted in the significant formation of 3-nitrotyrosine (3-NT), an in vivo marker of peroxynitrite generation, in the striatum and also caused a significant increase in the body temperature. METH injection also caused a significant decrease in the concentration of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) by 76%, 53% and 40%, respectively, in the striatum compared with the control group. Treatment with FeTMPyP blocked the formation of 3-NT by 66% when compared with the METH group. FeTMPyP treatment also provided significant protection against the METH-induced hyperthermia and depletion of DA, DOPAC and HVA. Administration of FeTMPyP alone neither resulted in 3-NT formation nor had any significant effect on DA or its metabolite concentrations. These findings indicate that peroxynitrite plays a role in METH-induced dopaminergic neurotoxicity and also suggests that peroxynitrite decomposition catalysts may be beneficial for the management of psychostimulant abuse. (C) 1999 Published by Elsevier Science B.V. All rights reserved.