Doxorubicin increases the susceptibility of brain mitochondria to Ca2+-induced permeability transition and oxidative damage
Doxorubicin increases the susceptibility of brain mitochondria to Ca2+-induced permeability transition and oxidative damage
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DOI：
10.1016/j.freeradbiomed.2008.08.008
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发表时间：
2008-11-15
影响因子：
7.4
通讯作者：
Moreira, Paula I.
中科院分区：
文献类型：
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作者：
Cardoso, Susana;Santos, Renato X.;Moreira, Paula I.
本研究旨在探讨亚慢性给药阿霉素（DOX）对脑线粒体生物能量学和氧化状态的影响。大鼠每周注射7次载体（sc，生理盐水溶液）或DOX (sc. 2 mg kg(-1))，最后一次给药1周后处死动物，获得脑线粒体组分。分析了几个参数：呼吸链。磷酸化系统，诱导渗透过渡孔（PTP），线粒体乌头酶活性，脂质过氧化市场，和非酶抗氧化防御。DOX处理导致硫代巴比妥酸反应物质和维生素E水平升高，还原性谷胱甘肽含量和乌头酸酶活性降低。此外，DOX增强了Ca2+诱导的PTP。其他参数分析无统计学差异。总之，我们的研究结果表明，DOX治疗增加了脑线粒体对Ca2+诱导的PTP开放和氧化应激的易感性，使脑细胞更易退化和死亡。(C) 2008爱思唯尔公司版权所有。
This Study was aimed at investigating the effects of subchronic administration of doxorubicin (DOX) on brain mitochondrial bioenergetics and oxidative status. Rats were treated with seven weekly injections of vehicle (sc, saline solution) or DOX (sc. 2 mg kg(-1)), and 1 week after the last administration of the drug the animals were sacrificed and brain mitochondrial fractions were obtained. Several parameters were analyzed: respiratory chain. phosphorylation system, induction of the permeability transition pore (PTP), mitochondrial aconitase activity, lipid peroxidation markets, and nonenzymatic antioxidant defenses. DOX treatment induced an increase in thiobarbituric acid-reactive Substances and vitamin E levels and a decrease in reduced glutathione content and aconitase activity. Furthermore, DOX potentiated PTP induced by Ca2+. No statistical differences were observed in the other parameters analyzed. Altogether Our results show that DOX treatment increases the susceptibility of brain mitochondria to Ca2+-induced PTP opening and oxidative stress, predisposing brain cells to degeneration and death. (C) 2008 Elsevier Inc. All rights reserved.