The Potential Protective Effects of Resveratrol Against Cabazitaxel-Induced Oxidative Stress and Cardiotoxicity in...

Cabazitaxel, an anti-prostate cancer agent, is associated with dose-dependent cardiotoxicity mediated by oxidative stress. This study investigated cabazitaxel-induced cardiac injury, the utility of intraventricular pressure gradients for early detection, and the potential protective effects of resveratrol. Twenty male Sprague Dawley rats were allocated into four groups: control, therapeutic cabazitaxel (0.5 mg/kg/week, intraperitoneally), toxic cabazitaxel (1.5 mg/kg/week, intraperitoneally), and toxic cabazitaxel + resveratrol (1.5 mg/kg/week cabazitaxel + 10 mg/kg/day resveratrol, intraperitoneally) for 28 days. Cardiac function was assessed via conventional echocardiography, electrocardiography, and intraventricular pressure gradients under anesthesia. Blood samples and heart tissues were collected for further biochemical and histopathological evaluation. Toxic cabazitaxel administration induced significant RR prolongation and bradycardia compared with controls (RR: 0.21 ± 0.02 vs. 0.18 ± 0.02 s; heart rate: 285.88 ± 31.04 vs. 330.40 ± 27.24 bpm), accompanied by aortic dilatation (aortic diameter: 3.73 ± 0.29 vs. 3.28 ± 0.21 mm), reduced acceleration time to ejection time ratio (0.21 ± 0.04 vs. 0.32 ± 0.12), increased derivatives of reactive oxygen metabolites: 394.75 ± 63.47 vs. 324.80 ± 15.56 U.CARR), elevated platelet counts (121.10 ± 26.48 vs. 81.65 ± 6.49 10⁴/µL), decreased hemoglobin levels (14.26 ± 2.02 vs. 17.66 ± 1.014 g/dL), along with structural myocardial damage. Resveratrol co-administration reduced derivatives of reactive oxygen metabolites (372.40 ± 33.02), normalized aortic diameter, and improved acceleration time to ejection time ratio (3.09 ± 0.40 mm; 0.28 ± 0.06), enhanced electrocardiographic parameters (RR: 0.17 ± 0.01 s; heart rate: 352.24 ± 20.567), restored hemoglobin and platelet counts (15.94 ± 1.39 g/dL; 98.38 ± 28.41 10⁴/µL), and preserved myocardial architecture. However, intraventricular pressure gradient indices remained elevated, and persistent thinning of the left ventricular posterior wall at end-diastole and end-systole was observed. These findings suggest that resveratrol partially mitigates cabazitaxel-induced cardiotoxicity.