2-Chloroacetaldehyde-induced脑谷胱甘肽耗竭和神经毒性。
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Sood C、O ' brien PJ
2-Chloroacetaldehyde-induced脑谷胱甘肽耗竭和神经毒性。
Br J癌症5。1996年7月,27日:s287 - 93。
- PubMed ID
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8763899 (在PubMed]
- 文摘
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2-Chloroacetaldehyde (CAA)形成在抗癌药物的代谢异环磷酰胺(IP)被卷入ifosfamide-related化疗期间神经毒性,但神经毒性机制是未知的。我们发现IP(900毫克公斤,订单)引起的嗜睡和温和的后肢瘫痪后6 h。神经毒性和IP-induced死亡率显著增强小鼠与苯巴比妥或地塞米松预处理诱导细胞色素P4503A。脑谷胱甘肽(GSH)含量也显著减少在这些老鼠进行预处理。2-Chloroethanol(92毫克公斤,i.p。) (CE)也引起脑谷胱甘肽降低50%后6 h政府老鼠。这个时候最大嗜睡和没碰CE-treated老鼠就非常明显。严重的后肢瘫痪发达国家和12至18 h后死亡了。之前大脑谷胱甘肽的耗竭2-cyclohexene-1-one大大加速CE-induced发病神经毒性表明大脑的谷胱甘肽的状态是一个重要的决定因素CE-induced神经毒性。此外,预处理与防治推迟CE-induced神经毒性和大脑谷胱甘肽耗竭。前由乙醇诱导脑但不是肝CYP2E1 CE的挑战也会加强CE-induced脑谷胱甘肽耗竭和神经毒性。肝脏谷胱甘肽耗竭影响表明CE-induced瘫痪是依赖于大脑而不是肝CYP2E1催化氧化CE创新艺人经纪公司。 Ethanol was neuroprotective even if given 60 min after CE and prevented further cerebral GSH depletion. 4-Methylpyrazole, a CYP2E1 and alcohol dehydrogenase inhibitor, prevented both CE-induced hepatic and cerebral GSH depletion and paralysis. This suggests that the neurotoxicity associated with IP chemotherapy involves activation of chloroethanol by cerebral CYP2E1 to chloroacetaldehyde which mediates cerebral GSH depletion. Neurotoxicity may be prevented by restoring cerebral GSH status and/or by preventing activation of CE by CYP2E1 with ethanol.
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