This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control (MQC), including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.

中文翻译：

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线粒体在阿霉素介导的心脏毒性中的作用：从分子机制到治疗策略

这篇全面的综述深入探讨了线粒体在阿霉素诱导的心脏毒性中的关键作用，这是限制这种有效的蒽环类化疗药物临床使用的一个重要并发症。阿霉素虽然能有效对抗各种恶性肿瘤，但与剂量依赖性心脏毒性有关，可能导致不可逆的心脏损伤。该综述仔细剖析了这种心脏毒性的分子机制，特别关注线粒体功能障碍，这是这种不良反应的核心因素。讨论的核心是线粒体质量控制（MQC）的概念，包括线粒体动力学（融合/裂变平衡）和线粒体自噬。该综述提供了证据，证明这些过程的异常与阿霉素治疗患者的心脏毒性有关。它阐明了阿霉素如何破坏线粒体动力学，导致线粒体裂变和融合之间的不平衡，并损害线粒体自噬，最终导致功能障碍线粒体的积累和随后的心肌细胞损伤。此外，该综述还探讨了针对线粒体功能障碍的新兴治疗策略。它强调了调节线粒体动力学和增强线粒体自噬以减轻阿霉素引起的心脏损伤的潜力。这些策略包括使用线粒体裂变抑制剂、融合促进剂和调节线粒体自噬的药物进行药物干预。该评论强调了临床前研究的有希望的结果，同时提倡进行更广泛的临床试验以在人类患者中验证这些方法。总之，这篇综述为线粒体功能障碍与阿霉素介导的心脏毒性之间的复杂关系提供了有价值的见解。它强调需要继续研究靶向线粒体疗法，作为改善阿霉素心脏安全性的一种手段，从而提高癌症患者的整体治疗结果。