Empagliflozin Mitigates Doxorubicin-Induced Cardiotoxicity in Rats: Electrocardiographic, Biochemical, and Histopathological Evidence

Doxorubicin (DOX) is a widely used anthracycline, but its clinical use is limited by dose-dependent cardiotoxicity. This experimental study evaluated the cardioprotective potential of empagliflozin (EMPA) against DOX-induced cardiotoxicity. Thirty healthy adult rats were randomized into five groups (n = 6): control (group I), EMPA (group II), EMPA + DOX (group III), DOX (group IV), and EMPA-preconditioning + DOX (group V). EMPA was administered orally at 10 mg/kg/day, either concomitantly with DOX or as a 14-day preconditioning course. Cumulative DOX exposure reached 15 mg/kg to establish a reproducible cardiotoxicity model. Serial electrocardiograms (ECGs) were recorded, blood samples were collected, and hearts were harvested for detailed histopathological analysis. Compared with the control group, group IV demonstrated significant QT/QTc prolongation and repolarization abnormalities, marked troponin elevation, and characteristic histological lesions, including cardiomyocyte vacuolization, loss of striations, diffuse inflammation, myocyte atrophy, and increased fibrosis. In groups receiving EMPA with DOX exposure (groups III and V), ECG changes were attenuated, troponin elevation was lower, and structural myocardial damage was substantially reduced, with better preservation of cardiomyocyte architecture and less fibrosis. These results suggest that EMPA provides significant cardioprotection against DOX-induced cardiotoxicity in rats, supporting further investigation of SGLT2 inhibitors in cardio-oncology.