GSTP1 Mitigates Doxorubicin-Induced Cardiomyopathy by Inhibiting Ferroptosis via JNK

GSTP1 alleviates doxorubicin-induced myocardial disease by inhibiting iron death through JNK. Doxorubicin (DOX), a widely used anticancer drug, is known to induce cardiomyopathy, a serious side effect that limits its clinical application. Ferroptosis, a recently identified form of regulated cell death characterized by iron-dependent lipid peroxidation, has been implicated in DOX-induced cardiomyopathy. In this study, we investigated the role of GSTP1, a key enzyme in glutathione metabolism, in protecting against DOX-induced cardiomyopathy by inhibiting ferroptosis through the JNK pathway. We found that GSTP1 expression was significantly reduced in DOX-treated cardiomyocytes, leading to increased ferroptosis and cardiomyopathy. Overexpression of GSTP1 attenuated DOX-induced ferroptosis and cardiomyopathy by inhibiting JNK activation. Furthermore, we demonstrated that GSTP1 directly interacts with JNK and inhibits its phosphorylation, thereby preventing JNK-mediated ferroptosis. Our findings suggest that GSTP1 is a potential therapeutic target for preventing DOX-induced cardiomyopathy. In conclusion, our study provides strong evidence that GSTP1 plays a crucial role in mitigating DOX-induced cardiomyopathy by inhibiting ferroptosis through JNK. This discovery has important implications for the development of novel therapeutic strategies to protect against DOX-induced cardiac toxicity.