Luteolin Alleviates Axitinib-Induced Cardiomyocyte Apoptosis in Mice

Axitinib, a tyrosine kinase inhibitor (TKI), is associated with a risk of cardiotoxicity in clinical practice. However, its underlying toxicological mechanisms remain unclear, and effective cardioprotective strategies are lacking. This study aims to investigate the mechanisms of axitinib-induced cardiac injury and evaluate the protective effects of luteolin. In this study, C57BL/6 mice were randomly divided into four groups: Control, Axitinib, Axitinib + Luteolin, and Luteolin alone. Ventricular systolic function (EF/FS/LVEDD/LVESD) was evaluated by echocardiography. Serum cardiac troponin T (cTnT) levels were measured to assess cardiotoxicity. Histopathological changes were observed via HE and Masson's trichrome staining. Myocardial apoptosis was quantified using TUNEL staining, and apoptosis-related proteins (Bax/Bcl2) were analyzed by Western blot. Reactive oxygen species (ROS) accumulation was evaluated using DHE staining. The results showed that compared with the control group, axitinib did not significantly alter echocardiographic parameters but significantly elevated serum cTnT levels, indicating subclinical cardiotoxicity. Furthermore, axitinib induced notable histopathological changes, promoted aberrant ROS accumulation, upregulated the Bax/Bcl2 ratio, and triggered cardiomyocyte apoptosis. Co-administration of luteolin significantly reduced ROS levels, restored the Bax/Bcl2 balance, and effectively alleviated axitinib-induced cardiotoxicity and apoptosis. In conclusion, axitinib induces subclinical cardiac injury by promoting ROS generation and disrupting the Bax/Bcl2 balance, thereby activating cardiomyocyte apoptosis. Luteolin exerts significant cardioprotective effects by suppressing ROS accumulation and rectifying apoptotic pathway dysregulation, providing a promising novel strategy for the prevention and treatment of targeted therapy-induced cardiotoxicity.