Rutin and Glimepiride Combination: A Novel Approach for Managing Diabetes Nephropathy in Streptozotocin Induced Diabetes in Wistar Rats

Background: Diabetes mellitus remains a global health concern, because of its associated complications, including diabetic nephropathy. Glimepiride, a sulfonylurea derivative, and rutin, a flavonoid with antioxidant properties, have shown potential in managing diabetic complications. This study was aimed at investigating the therapeutic efficacy of these treatments, individually or in combination, against streptozotocin (STZ)-induced diabetic complications in albino rats (Rattus norvegicus). Methods: Diabetes was induced by intraperitoneal injection of STZ at 55 mg/kg in Wistar rats of both sexes weighing 200–250 g. Rats with serum glucose (Glu) levels ≥250 mg/dL were selected for pharmacological assessment. The diabetic rats were divided into six groups, each comprising six rats, receiving the following treatments: GLP alone at 0.5 mg/kg, rutin alone at 50 mg/kg or 100 mg/kg, and combinations of GLP with rutin. Treatments were administered over 45 days. Physiological parameters, serum markers (including Glu and lipid profiles), inflammatory cytokines, renal hypertrophy, oxidative stress markers, and histopathological changes in kidney tissues were evaluated to assess treatment effects. Result: Significant improvements were observed in rats treated with GLP, rutin, or both, including decreased diabetes-induced weight loss, and increased glycemic control with lower serum Glu levels. Favorable changes in lipid profiles and significant decreases in inflammatory cytokines indicated systemic improvements. Moreover, the treatments markedly decreased renal hypertrophy, thus suggesting enhanced renal function. Histopathological analysis indicated that combination therapy, compared with individual treatments, markedly decreased tubular dilation and preserved renal architecture, thus highlighting synergistic benefits in managing diabetic complications, particularly diabetic nephropathy. Conclusion: Our findings suggest that GLP and rutin, individually or in combination, hold promise in managing diabetic nephropathy, according to an STZ-induced diabetic rat model. The combination therapy demonstrated synergistic benefits, particularly in preserving renal architecture and decreasing tubular dilation. These results highlight a potential therapeutic strategy for alleviating diabetes-induced renal complications, and emphasize the importance of exploring combined approaches in diabetic management to enhance treatment efficacy and patient outcomes.