Adriamycin-induced oxidative mitochondrial cardiotoxicity
Adriamycin-induced oxidative mitochondrial cardiotoxicity
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DOI：
10.1007/s10565-006-0140-y
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发表时间：
2007-01-01
影响因子：
6.1
通讯作者：
Wallace, K. B.
中科院分区：
文献类型：
--
作者：
Berthiaume, J. M.;Wallace, K. B.
抗癌剂阿霉素(ADR)长期以来一直被认为具有剂量限制性的心脏毒性。许多研究试图描述和阐明其心脏毒性作用背后的机制(S)。尽管有大量数据涵盖了该药物介导的广泛影响，但确切的机制仍存在争议。然而，人们一致认为这种毒性与活性氧自由基(ROS)的诱导有关。ADR通过药物在电子传递链复合体I处的氧化还原循环来诱导心脏中的ROS。许多研究支持这一理论，即线粒体是ADR诱导的氧化应激的主要目标，无论是急性还是长期的。本文综述了ADR氧化还原循环对线粒体的影响，支持这些细胞器确实是ADR心脏毒性的主要因素的假说。本综述侧重于利用具有临床相关剂量或浓度的ADR的心脏模型进行的研究，以期促进我们对ADR毒性机制的理解。这种对当前数据的汇编可能会为开发更好地定制以最大限度地减少ADR的剂量限制效应的治疗策略提供有价值的见解。
The anticancer agent Adriamycin (ADR) has long been recognized to induce a dose-limiting cardiotoxicity. Numerous studies have attempted to characterize and elucidate the mechanism(s) behind its cardiotoxic effect. Despite a wealth of data covering a wide-range of effects mediated by the drug, the definitive mechanism remains a matter of debate. However, there is consensus that this toxicity is related to the induction of reactive oxygen species (ROS). Induction of ROS in the heart by ADR occurs via redox cycling of the drug at complex I of the electron transport chain. Many studies support the theory that mitochondria are a primary target of ADR-induced oxidative stress, both acutely and long-term. This review focuses on the effects of ADR redox cycling on the mitochondrion, which support the hypothesis that these organelles are indeed a major factor in ADR cardiotoxicity. This review has been constructed with particular emphasis on studies utilizing cardiac models with clinically relevant doses or concentrations of ADR in the hope of advancing our understanding of the mechanisms of ADR toxicity. This compilation of current data may reveal valuable insights for the development of therapeutic strategies better tailored to minimizing the dose-limiting effect of ADR.