文献类型：期刊文献

英文题名：Ferroptosis regulation in doxorubicin-induced cardiotoxicity: multi-mechanism interventions and translational strategies

作者：Chen, XiaoJie[1,2];Lu, YuYuan[1];Wang, YiYuan[1];Kou, YuShun[1];Gu, YuanHui[3];Yi, Lin[1,4]

第一作者：陈雪娟;Chen, XiaoJie

通信作者：Yi, L[1];Yi, L[2]

机构：[1]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[2]Gansu Prov Hosp, Lab Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[3]Gansu Prov Hosp, Dept Gen Surg, Lanzhou, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Chron Dis Lab, Lanzhou, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Chron Dis Lab, Lanzhou, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：17

外文期刊名：FRONTIERS IN PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001821190200001)】；

基金：The author(s) declared that financial support was received for this work and/or its publication. This work was supported by grants from Science and Technology Program of Lanzhou Chengguan District, No. 2025-ZC-32; Gansu Provincial Traditional Chinese Medicine Scientific Research Project, No. GZKZ-2025-56; General Program of the Joint Scientific Research Fund, No. 23JRRA1521; Open Subjects of Dunhuang Medicine in the Key Laboratory of Translation of the Ministry of Education, No. DHYX23-07; Science and Technology Fund Program of Gansu Province, No. 24JRRA590; Science and Technology Fund Program of Gansu Province, No. 24JRRA598; Guiding Program of the Lanzhou Municipal Bureau of Science and Technology, No. 2023-ZD-32; Research Project of Gansu Provincial Hospital, No. 25GSSYG-4.

语种：英文

外文关键词：doxorubicin-induced cardiotoxicity; ferroptosis; gut microbiota-heart axis; phytochemicals; tissue-targeted intervention

摘要：Doxorubicin (DOX), a highly effective anthracycline chemotherapy drug, has its clinical application severely restricted by dose-dependent doxorubicin-induced cardiotoxicity (DIC). Ferroptosis, an iron-dependent, lipid peroxidation-driven regulated cell death, has been confirmed as a core pathological mechanism in DIC, where it synergistically participates with multiple cell death modalities in myocardial injury. This review systematically elaborates the multidimensional molecular mechanisms underlying DOX-induced myocardial ferroptosis, including: lipid peroxidation cascade self-amplification, bidirectional regulation by selective autophagy, multilayered GPX4 modification and stability regulation, and involvement of the gut microbiota-heart axis. Concurrently, we summarize evidence for natural phytochemicals-including flavonoids, polyphenols, terpenoids, and traditional Chinese medicine compounds-that inhibit myocardial ferroptosis via multi-target mechanisms, providing theoretical support for phytochemical-based DIC intervention. Critically, this review addresses the clinical translation dilemmas in ferroptosis regulation and proposes three innovative strategies: (1) time-decoupling strategy based on IFN-gamma signaling; (2) cardiac-targeted nanodrug delivery system employing the OGF/OGFR axis; (3) cross-regulation between ferroptosis and other regulated cell death pathways. These strategies aim to achieve tissue-selective ferroptosis intervention, simultaneously protecting myocardium while maintaining DOX anti-tumor efficacy, thereby providing molecular mechanistic basis and clinical translational directions for constructing precision ferroptosis-targeted cardioprotective strategies.