Methamphetamine-induced changes in antioxidant enzymes and lipid peroxidation in copper/zinc-superoxide dismutase transgenic mice

Methamphetamine-induced changes in antioxidant enzymes and lipid peroxidation in copper/zinc-superoxide dismutase transgenic mice
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DOI:
10.1111/j.1749-6632.1998.tb08224.x
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发表时间:
1998-01-01
期刊:
NEUROCHEMISTRY OF DRUGS OF ABUSE
影响因子:
--
通讯作者:
Cadet, JL
Cadet, JL
中科院分区:
其他
文献类型:
--
作者:
Jayanthi, S;Ladenheim, B;Cadet, JL

文献摘要

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本研究旨在调查甲基苯丙胺(METH)诱导的毒性对大脑皮质和纹状体抗氧化防御系统的影响。由于冰毒诱导的毒性在铜/锌超氧化物歧化酶转基因 (Cu/Zn-SOD-Tg) 小鼠中减弱,因此我们试图确定与非 Tg 小鼠相比,冰毒对这些小鼠的抗氧化酶是否有不同的影响。 METH (4 x 10 mg/kg) 诱导皮质区域 Cu/Zn-SOD 活性显着降低,但不改变非 Tg 小鼠的纹状体酶活性;而纯合 SOD-Tg 小鼠的纹状体显着增加。此外,METH 还导致非 Tg 小鼠纹状体中过氧化氢酶 (CAT) 活性降低,而纯合 SOD-Tg 小鼠皮质中过氧化氢酶 (CAT) 活性显着增加。 METH 还诱导非 Tg 小鼠的皮质和纹状体区域以及杂合 SOD-TO 小鼠的纹状体中谷胱甘肽过氧化物酶 (GSH-Px) 的减少。非 Tg 和杂合子 SOD-Tg 小鼠的皮质和纹状体中脂质过氧化均增加,而纯合子 SOD-Tg 小鼠则不受影响。这些结果在术语中进行了讨论,它们证实了氧自由基在冰毒诱导的啮齿动物毒性中的作用。
The present study was conducted to investigate the effects of methamphetamine (METH)-induced toxicity on brain cortical and striatal antioxidant defense systems. Because METH-induced toxicity is attenuated in copper/zinc-superoxide dismutase transgenic (Cu/Zn-SOD-Tg) mice, we sought to determine.if METH had differential effect on antioxidant enzymes on these mice in comparison to non-Tg mice. METH (4 x 10 mg/kg) induced a significant decrease in Cu/Zn-SOD activity in the cortical region without altering striatal enzymatic activity in non-Tg mice; whereas homozygous SOD-Tg mice showed a significant increase in the striatum. In addition, METH caused decrease in catalase (CAT) activity in the striatum of non-Tg mice and significant increase in the cortex of homozygous SOD-Tg mice. METH also induced decreases in glutathione peroxidase (GSH-Px) in both cortical and striatal regions of non-Tg mice and in the striatum of heterozygous SOD-TO mice. Lipid peroxidation was increased in both cortices and striata of non-Tg and heterozygous SOD-Tg mice, whereas the homozygous SOD-Tg mice were not affected. These results are discussed in term!, of their substantiation of a role for oxygen-based radicals in METH-induced toxicity hi rodents.