Abstract
BACKGROUND: As a leading cause of global morbidity, myocardial infarction (MI) is a primary focus of medical research. The isoproterenol (ISO)-induced model of cardiac injury is a cornerstone of this work, providing a validated experimental system that simulates the human condition. This study investigated the cardioprotective potential of dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, against ISO-induced myocardial injury in adult male rats. MATERIALS AND METHODS: Thirty-two rats were divided into four groups; Control group, DAPA-only group: DAPA (1 mg/kg/day, orally, 14 days) + saline, ISO-only: Saline (orally, 14 days) + ISO (100 mg/kg/day, days 13-14) and fourth group, DAPA + ISO: pretreated with DAPA 1 mg/kg/day orally) for 14 days, followed by ISO 100 mg/kg, subcutaneously days 13-14. DAPA's protective effects against ISO-induced MI were evaluated by assessing cardiac damage by measuring serum biomarkers of heart injury while simultaneously evaluating oxidative stress through lipid peroxidation levels and antioxidant activity in cardiac tissue. Histopathological examination revealed structural changes in myocardial tissue, complemented by molecular analysis quantifying the expression of key apoptotic regulators. RESULTS: Biochemical analysis revealed that DAPA significantly reduced ISO-induced elevations in cardiac troponin-I, creatine kinase-MB, lactate dehydrogenase, and oxidative stress markers; malondialdehyde, superoxide dismutase, and reduced glutathione. DAPA also attenuated inflammatory cytokines: tumor necrosis factor-alpha and interleukin-6 (IL-6). Histopathological examination of heart tissues demonstrated that DAPA mitigated ISO-induced myocardial necrosis and inflammatory infiltration, preserving cardiac architecture. Moreover, DAPA downregulated the pro-apoptotic protein (Bax) expression and upregulated the anti-apoptotic protein (Bcl2) levels in the heart. CONCLUSIONS: These findings suggest that DAPA exerts multimodal cardio-protection beyond its antidiabetic action, positioning it as a promising adjunct therapy for ischemic heart disease. Further clinical studies are warranted to validate its translational potential.