EVALUATION OF THE EFFECT OF DAPAGLIFLOZIN, OMEPRAZOLE, AND THEIR COMBINATION ON DIABETIC NEPHROPATHY IN RATS

Diabetic nephropathy (DN) is a serious complication of Type 2 diabetes mellitus (T2DM), driven by inflammation and oxidative stress. This study evaluated the therapeutic potential of dapagliflozin, omeprazole, and their combination on DN using a streptozotocin-nicotinamide-induced T2DM model in Wistar rats. Forty-two male rats were divided into seven groups: Group I: Normal control rats, Group II: Normal rats treated with dapagliflozin (3 mg/kg/day, orally), Group III: Normal rats treated with omeprazole (40 mg/kg/day, orally), Group IV: Diabetic control rats, Group V: Diabetic rats treated with dapagliflozin, Group VI: Diabetic rats treated with omeprazole, and Group VII: Diabetic rats treated with a combination of dapagliflozin and omeprazole. Treatments lasted four weeks. Biochemical, histopathological, and immunohistochemical assessments were conducted to evaluate renal function, inflammatory cytokines, oxidative stress, and NF-κB expression. Dapagliflozin significantly improved glycemic control, kidney function (serum creatinine, BUN, and albuminuria), and reduced pro-inflammatory cytokines (TNF-α, IL-6) and oxidative stress markers (MDA, SOD, TAC). Histologically, it attenuated glomerular and interstitial damage. Omeprazole alone showed mild anti-inflammatory and antioxidant effects without significant improvement in renal function or structure. The combination therapy led to further reduction in NF-κB expression compared to dapagliflozin alone, although without added functional or structural benefit. These results suggest that dapagliflozin is effective in mitigating DN through its anti-hyperglycemic, anti-inflammatory, and antioxidant effects, while omeprazole may modestly enhance its anti-inflammatory action. The findings support the role of SGLT2 inhibitors as a cornerstone in DN management, with PPIs offering limited adjunctive value.