靶向线粒体的小分子:对抗多柔比星诱导的心脏毒性的机制方法

IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Chinmay Pal
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引用次数: 0

摘要

多柔比星(Dox)是一种常用的化疗药物,对多种癌症有效,但其临床应用却受到剂量依赖性和累积性心脏毒性的极大限制。线粒体功能障碍被认为是 Dox 引起心脏毒性的关键因素,会导致氧化应激、钙平衡紊乱和凋亡途径激活。最近的研究强调了特异性靶向线粒体的小分子药物缓解这些有害影响的潜力。本综述全面分析了在多柔比星诱导的心脏毒性(DIC)情况下,通过保护线粒体功能来提供心脏保护的小分子药物。其作用机制包括减少活性氧(ROS)的产生、稳定线粒体膜电位、增强线粒体的生物生成以及调节参与细胞存活和凋亡的关键信号通路。通过靶向线粒体,这些小分子为预防或减轻与多克斯治疗相关的心脏毒性效应提供了一种前景广阔的治疗策略。这篇综述不仅讨论了这些药物的作用机制,还强调了它们在改善癌症患者心血管预后方面的潜力。深入了解这些机制有助于制定更有效的策略,在化疗期间保护心脏,从而使患者在持续使用 Dox 的同时降低心血管健康风险。这篇综述强调了线粒体靶向疗法的关键作用,认为它是解决 DIC 的一种有前途的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Small Molecules Targeting Mitochondria: A Mechanistic Approach to Combating Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (Dox) is a commonly used chemotherapy drug effective against a range of cancers, but its clinical application is greatly limited by dose-dependent and cumulative cardiotoxicity. Mitochondrial dysfunction is recognized as a key factor in Dox-induced cardiotoxicity, leading to oxidative stress, disrupted calcium balance, and activation of apoptotic pathways. Recent research has emphasized the potential of small molecules that specifically target mitochondria to alleviate these harmful effects. This review provides a comprehensive analysis of small molecules that offer cardioprotection by preserving mitochondrial function in the context of doxorubicin-induced cardiotoxicity (DIC). The mechanisms of action include the reduction of reactive oxygen species (ROS) production, stabilization of mitochondrial membrane potential, enhancement of mitochondrial biogenesis, and modulation of key signaling pathways involved in cell survival and apoptosis. By targeting mitochondria, these small molecules present a promising therapeutic strategy to prevent or reduce the cardiotoxic effects associated with Dox treatment. This review not only discusses the mechanistic actions of these agents but also emphasizes their potential in improving cardiovascular outcomes for cancer patients. Gaining insight into these mechanisms can help in creating more effective strategies to safeguard the heart during chemotherapy, allowing for the ongoing use of Dox with a lower risk to the patient's cardiovascular health. This review highlights the critical role of mitochondria-targeted therapies as a promising approach in addressing DIC.

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来源期刊
Cardiovascular Toxicology
Cardiovascular Toxicology 医学-毒理学
CiteScore
6.60
自引率
3.10%
发文量
61
审稿时长
>12 weeks
期刊介绍: Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.
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