Laboratory of Cellular and Molecular Cardiovascular Physiology, Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy.
Laboratory of Organ and System Physiology, Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy.
Antioxid Redox Signal. 2020 May 20;32(15):1081-1097. doi: 10.1089/ars.2020.8016. Epub 2020 Feb 10.
Despite their serious side effects, anthracyclines (ANTs) are the most prescribed chemotherapeutic drugs because of their strong efficacy in both solid and hematological tumors. A major limitation to ANTs clinical application is the severe cardiotoxicity observed both acutely and chronically. The mechanism underlying cardiac dysfunction under chemotherapy is mainly dependent on the generation of oxidative stress and systemic inflammation, both of which lead to progressive cardiomyopathy and heart failure. Over the years, the iatrogenic ANTs-induced cardiotoxicity was believed to be simply given by iron metabolism and reactive oxygen species production; however, several experimental data indicate that ANTs may use alternative damaging mechanisms, such as topoisomerase 2β inhibition, inflammation, pyroptosis, immunometabolism, and autophagy. In this review, we aimed at discussing ANTs-induced cardiac injury from different points of view, updating and focusing on oxidative stress and inflammation, since these pathways are not exclusive or independent from each other but they together importantly contribute to the complexity of ANTs-induced multifactorial cardiotoxicity. A deeper understanding of the mechanistic signaling leading to ANTs side effects could reveal crucial targeting molecules, thus representing strategic knowledge to promote better therapeutic efficacy and lower cardiotoxicity during clinical application.
尽管蒽环类药物（ANTs）具有严重的副作用，但由于它们在实体瘤和血液系统肿瘤中的强大疗效，仍是应用最广泛的化疗药物。ANTs 临床应用的主要限制是其在急性和慢性时均观察到的严重心脏毒性。化疗引起心脏功能障碍的机制主要依赖于氧化应激和全身炎症的产生，这两者均导致进行性心肌病和心力衰竭。多年来，人们认为医源性 ANTs 诱导的心脏毒性主要是由铁代谢和活性氧产生引起的；然而，一些实验数据表明，ANTs 可能采用替代的损伤机制，如拓扑异构酶 2β 抑制、炎症、细胞焦亡、免疫代谢和自噬。在这篇综述中，我们旨在从不同角度讨论 ANTs 诱导的心脏损伤，更新并重点关注氧化应激和炎症，因为这些途径不是相互排斥或独立的，而是共同对 ANTs 诱导的多因素心脏毒性的复杂性产生重要影响。深入了解导致 ANTs 副作用的机制信号可能会揭示关键的靶向分子，从而为临床应用中提高治疗效果和降低心脏毒性提供重要的知识。
