Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (Ecstasy).
Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (Ecstasy).
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转基因小鼠中人铜/锌超氧化物歧化酶的过度表达可减轻亚甲二氧基甲基苯丙胺（摇头丸）引起的氧化应激。
DOI：
10.1016/s0306-4522(98)00698-8
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发表时间：
1999
期刊：
影响因子：
3.3
通讯作者：
Cadet,JL
中科院分区：
文献类型：
--
作者：
Jayanthi,S;Ladenheim,B;Andrews,AM;Cadet,JL
对非转基因CD-1小鼠给予3，4-亚甲二氧基甲基苯丙胺（4× 20 mg/kg）可导致尾壳核中多巴胺、3，4-二羟基苯乙酸和5-羟色胺显著耗竭。海马和额叶皮质中的多巴胺能标记物没有显著变化。纯合子和杂合子铜/锌超氧化物歧化酶转基因小鼠显示对3，4-亚甲二氧基甲基苯丙胺对纹状体多巴胺能标记物的毒性作用的部分保护。此外，3，4-亚甲二氧基甲基苯丙胺注射导致铜/锌超氧化物歧化酶活性在额叶皮质，尾壳核和野生型小鼠海马体的显着下降。此外，伴随着3，4-亚甲二氧基甲基苯丙胺诱导的尾壳核和海马中过氧化氢酶活性降低，额叶皮质中谷胱甘肽过氧化物酶活性降低以及野生型小鼠额叶皮质、尾壳核和海马中脂质过氧化反应增加。与此相反，管理的3，4-亚甲二氧基甲基苯丙胺的纯合子超氧化物歧化酶转基因小鼠的抗氧化酶活性，也没有在脂质过氧化作用的显着变化。这些结果进一步证实了氧自由基在3，4-亚甲二氧基甲基苯丙胺诱导的神经毒性中的作用。目前的数据还表明，在3，4-亚甲二氧基甲基苯丙胺管理过程中产生的自由基可能会扰乱抗氧化酶。因此。可能会进一步产生过量的自由基，伴随着对细胞膜的过氧化损伤和相关的终末变性。
Administration of 3,4-methylenedioxymethamphetamine (4×20mg/kg) to non-transgenic CD-1 mice caused marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and 5-hydroxytryptamine in the caudate–putamen. There were no significant changes in serotonergic markers in the hippocampus and frontal cortex. Homozygous and heterozygous copper/zinc superoxide dismutase transgenic mice show partial protection against the toxic effects of 3,4-methylenedioxymethamphetamine on striatal dopaminergic markers. In addition, 3,4-methylenedioxymethamphetamine injections caused marked decreases in copper/zinc superoxide dismutase activity in the frontal cortex, caudate–putamen and hippocampus of wild-type mice. Moreover, there were concomitant 3,4-methylenedioxymethamphetamine-induced decreases in catalase activity in the caudate–putamen and hippocampus, decreases in glutathione peroxidase activity in the frontal cortex as well as increases in lipid peroxidation in the frontal cortex, caudate–putamen, and hippocampus of wild-type mice. In contrast, administration of 3,4-methylenedioxymethamphetamine to homozygous superoxide dismutase transgenic mice caused no significant changes in antioxidant enzyme activities nor in lipid peroxidation. These results provide further substantiation of a role for oxygen-based radicals in 3,4-methylenedioxymethamphetamine-induced neurotoxicity. The present data also suggest that free radicals generated during 3,4-methylenedioxymethamphetamine administration may perturb antioxidant enzymes. Consequently. there might be further overproduction of free radicals with associated peroxidative damage to cell membranes and associated terminal degeneration.