The effects of methamphetamine on the production of free radicals and oxidative stress.
The effects of methamphetamine on the production of free radicals and oxidative stress.
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发表时间：
1998-10
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通讯作者：
Bryan K. Yamamoto;Wenjun Zhu
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作者：
Bryan K. Yamamoto;Wenjun Zhu
甲基苯丙胺（METH）对促氧化过程和活性氧的产生的影响进行了研究，在体内大鼠脑。纹状体中的氧化损伤的存在下，所揭示的脂质的氧化，也通过脂质过氧化产物丙二醛的测量进行了评估。为了进一步阐明介导MET诱导的氧化应激的机制，我们研究了抗氧化剂通过铁螯合和捕获自由基对长期MET诱导的纹状体多巴胺含量降低的可能逆转。与盐水注射对照大鼠相比，METH四次注射方案后1小时而不是24小时杀死的大鼠纹状体中的尿酸浓度显著增加。METH增加了水杨酸和d-苯丙氨酸的羟基化产物的体内形成，这分别由2，3-二羟基苯甲酸和p-酪氨酸的升高的细胞外浓度证明。用铁螯合剂deferroxamine局部灌注纹状体，可减弱METH产生的纹状体多巴胺含量的长期消耗。在其他实验中，在孵育的纹状体匀浆丙二醛浓度升高显着的甲基处理的大鼠。最后，预处理与自旋捕获剂苯丁基硝酮之前，METH注射衰减随后的长期消耗纹状体多巴胺含量。总体而言，结果表明，甲基增加促氧化过程，并提供支持性证据，甲基产生氧化损伤。这些研究还表明，铁可能参与介导的长期损害多巴胺神经元后，重复管理的METH。
The effects of methamphetamine (METH) on pro-oxidant processes and on the production of reactive oxygen species were examined in vivo in the rat brain. The presence of oxidative damage in striatum, as revealed by the oxidation of lipid, also was assessed via the measurement of the lipid peroxidation product malonyldialdehyde. To elucidate further the mechanisms mediating METH-induced oxidative stress, we studied the possible reversal of the long-term METH-induced decrease in striatal dopamine content by antioxidants through iron chelation and trapping of free radicals. The uric acid concentration in the striata of rats killed 1 hr, but not 24 hr, after a four-injection regimen of METH was increased significantly compared with saline-injected control rats. METH increased the in vivo formation of the hydroxylated products of salicylate and d-phenylalanine, as evidenced by the elevated extracellular concentrations of 2,3 dihydroxybenzoic acid and p-tyrosine, respectively. The local perfusion of the striatum with the iron chelator deferroxamine attenuated the long-term depletions of striatal dopamine content produced by METH. In other experiments, malonyldialdehyde concentrations in incubated striatal homogenates were elevated significantly in METH-treated rats. Finally, pretreatment with the spin trapping agent phenylbutylnitrone before the METH injections attenuated the subsequent long-term depletions in striatal dopamine content. Overall, the results illustrate that METH increases pro-oxidant processes and offer supportive evidence that METH produces oxidative damage. These studies also demonstrate that iron may be involved in mediating the long-term damage to dopamine neurons after repeated administrations of METH.