Renoprotective Effect of Dapagliflozin and Valproic Acid on STZ Induce Diabetic Nephropathy in Wister Rats

Abstract

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus, leading to chronic kidney disease and end-stage renal failure. Current therapies only slow progression but do not reverse renal damage. The present study was designed to evaluate the renoprotective potential of dapagliflozin (SGLT2 inhibitor) and valproic acid (HDAC inhibitor with antioxidative and anti-inflammatory activity), individually and in combination, in streptozotocin (STZ)-induced diabetic nephropathy in Wistar rats. Experimental diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg). Animals were divided into six groups: normal control, diabetic control, standard drug-treated, dapagliflozin-treated, valproic acid-treated, and combination-treated groups. Treatments were continued for 8 weeks. Parameters assessed included fasting blood glucose, body weight, renal function markers (serum creatinine, urea, uric acid, BUN), oxidative stress markers (SOD, CAT, GSH, MDA), inflammatory cytokines, and histopathological examination of renal tissue. Results showed significant renal impairment in diabetic control rats, with elevated serum creatinine, urea, BUN, and marked histopathological changes. Dapagliflozin and valproic acid treatment significantly improved renal parameters, attenuated oxidative stress, and preserved histological architecture. Combination therapy demonstrated greater renoprotective efficacy compared to monotherapy. The study concludes that dapagliflozin and valproic acid possess complementary renoprotective actions, suggesting potential for combination therapy in diabetic nephropathy management.

Keywords: Diabetic nephropathy, dapagliflozin, valproic acid, Wistar rats, oxidative stress, renoprotection.