Eriodictyol Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Ferroptosis through Targeting FABP4

Doxorubicin (DOX), while an effective chemotherapeutic agent, is often associated with severe cardiotoxicity, significantly limiting its clinical use. Recent studies suggest that ferroptosis, a regulated form of cell death, plays a critical role in DOX-induced cardiac injury. Eriodictyol (ERD), a naturally occurring flavonoid compound abundantly found in citrus fruits and certain traditional Chinese herbs, has demonstrated promising cardioprotective properties; however, whether ERD can ameliorate DOX-induced cardiac injury and the underlying mechanisms of its action remain unexplored. In this study, a model of DOX-induced cardiotoxicity was established using C57BL/6 mice and H9c2 cells to investigate the cardioprotective effects of ERD. ERD treatment significantly reduced ferroptosis, alleviated mitochondrial damage and improved cardiac function. Further studies revealed that ERD may target fatty acid-binding protein 4 (FABP4) to exert its effects. Functional experiments confirmed that FABP4 knockdown impaired the protective effects of ERD, highlighting its essential role in ferroptosis inhibition. These findings indicate that ERD protects against DOX-induced cardiotoxicity primarily through the modulation of FABP4 and ferroptosis pathways, offering a potential therapeutic strategy for mitigating DOX-related adverse effects.