Pharmacological Evaluation of Bexagliflozin Monotherapy and Combination Therapy with Rutin in Streptozotocin-Induced Diabetes-Associated Cardiac Injury in Rats

Diabetes-associated cardiac injury is a distinct cardiac complication of diabetes mellitus characterized by metabolic derangements, oxidative stress, and myocardial remodeling independent of hypertension or coronary artery disease. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardioprotective effects beyond glycemic control. Type 2 diabetes was induced in Wistar rats using a high-fat diet for 4 weeks followed by a single low-dose streptozotocin (35 mg/kg, i.p.). Diabetic rats were treated for 8 weeks with Bexagliflozin (3 or 7 mg/kg), rutin (50 mg/kg), their combination, or metformin (200 mg/kg). Glycemic indices, serum insulin, cardiac injury biomarkers (CK-MB, LDH, Troponin-T), oxidative stress parameters (GSH, SOD, catalase, MDA), and histopathological alterations were evaluated. Diabetic control rats showed significant hyperglycemia, hypoinsulinemia, elevated cardiac biomarkers, increased lipid peroxidation, and marked myocardial disorganization ( p < 0.001 vs. normal). Bexagliflozin (7 mg/kg) significantly reduced fasting glucose, improved insulin levels, attenuated CK-MB and LDH elevations, enhanced antioxidant enzyme activity, and showed qualitative improvement in myocardial histopathological features ( p < 0.05 vs. diabetic control). Combination therapy demonstrated comparable cardioprotective effects, particularly in oxidative stress parameters, although higher-dose Bexagliflozin monotherapy showed comparable improvement in selected biomarkers. Bexagliflozin effectively attenuates biochemical and histopathological alterations associated with diabetes-induced cardiac injury in experimental diabetes induced cardiac inury. The combination with rutin demonstrated comparable effects in selected parameters and antioxidant benefit, supporting further translational investigations.