GSTP1 Protects Against Doxorubicin-Induced Cardiomyopathy by Inhibiting Ferroptosis Through JNK

GSTP1 alleviates DOX-induced myocardial injury by inhibiting iron death through JNK. Doxorubicin (DOX) is a widely used anticancer drug, but its clinical application is limited by cardiotoxicity. Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, has been implicated in DOX-induced cardiomyopathy. GSTP1, a glutathione S-transferase enzyme, has been shown to play a protective role in various diseases. This study aimed to investigate the role of GSTP1 in DOX-induced cardiomyopathy and its potential mechanism. We found that GSTP1 expression was decreased in DOX-treated cardiomyocytes and hearts, and its overexpression attenuated DOX-induced cardiomyocyte death. Mechanistically, GSTP1 inhibited ferroptosis by suppressing JNK activation and downstream signaling. Furthermore, GSTP1 knockdown exacerbated DOX-induced cardiomyopathy and enhanced ferroptosis. These findings suggest that GSTP1 protects against DOX-induced cardiomyopathy by inhibiting ferroptosis through the JNK signaling pathway. Targeting GSTP1 may provide a novel therapeutic strategy for DOX-induced cardiotoxicity.