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Background <p>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.</p> Methods <p>Type 2 diabetes was induced in Wistar rats using a high-fat diet for 4 weeks followed by a single low-dose streptozotocin (35&#xa0;mg/kg, i.p.). Diabetic rats were treated for 8 weeks with Bexagliflozin (3 or 7&#xa0;mg/kg), rutin (50&#xa0;mg/kg), their combination, or metformin (200&#xa0;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.</p> Results <p>Diabetic control rats showed significant hyperglycemia, hypoinsulinemia, elevated cardiac biomarkers, increased lipid peroxidation, and marked myocardial disorganization (<i>p</i> &lt; 0.001 vs. normal). Bexagliflozin (7&#xa0;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 (<i>p</i> &lt; 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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年7月14日

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  • Shradha Shaili,
  • Faiz Qamar,
  • Manju Sharma

摘要

Background

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.

Methods

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.

Results

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.

Conclusion

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.