Department of Burns & Plastic and Wound Repair, Ganzhou People's Hospital, Ganzhou, Jiangxi 341000, China.
Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China.
Int J Biochem Cell Biol. 2024 Sep;174:106632. doi: 10.1016/j.biocel.2024.106632. Epub 2024 Jul 23.
Doxorubicin (DOX) is an anti-tumor agent for chemotherapy, but its use is often hindered by the severe and life-threatening side effect of cardiovascular toxicity. In recent years, studies have focused on dysregulated iron metabolism and ferroptosis, a unique type of cell death induced by iron overload, as key players driving the development of DOX-induced cardiotoxicity (DIC). Recent advances have demonstrated that DOX disturbs normal cellular iron metabolism, resulting in excessive iron accumulation and ferroptosis in cardiomyocytes. This review will explore how dysregulated iron homeostasis and ferroptosis drive the progression of DIC. We will also discuss the current approaches to target iron metabolism and ferroptosis to mitigate DIC. Besides, we will discuss the limitations and challenges for clinical translation for these therapeutic regimens.
阿霉素（DOX）是一种用于化疗的抗肿瘤药物，但由于其严重的、危及生命的心血管毒性副作用，其应用常常受到限制。近年来，研究集中在失调的铁代谢和铁死亡上，铁死亡是一种由铁过载诱导的独特的细胞死亡类型，是导致阿霉素诱导的心脏毒性（DIC）的关键因素。最近的研究表明，DOX 扰乱正常的细胞内铁代谢，导致心肌细胞中铁蓄积过多和铁死亡。本综述将探讨失调的铁稳态和铁死亡如何驱动 DIC 的进展。我们还将讨论针对铁代谢和铁死亡来减轻 DIC 的当前方法。此外，我们还将讨论这些治疗方案在临床转化中的局限性和挑战。
