Evaluation of the protective effects of liraglutide, dapagliflozin and their combination in rat kidneys of streptozotocin induced diabetes.

AIM: To compare the effects of liraglutide, dapagliflozin, and their combination on renal inflammation, oxidative stress, and fibrosis in streptozotocin (STZ)-induced diabetes in rats. METHODS: Adult Wistar rats were divided into five groups (15-17 rats/group): control; diabetes (DM, single intraperitoneal STZ 50 mg/kg); dapagliflozin-treated diabetes (Dapa, 1 mg/kg orally); liraglutide-treated diabetes (Lira, 0.4 mg/kg subcutaneously); and combined treatment (Dapa+Lira). Treatments were administered for 8 weeks. RESULTS: Dapagliflozin and/or liraglutide treatments reduced glucose levels, with the strongest reduction in the combined group. Diabetes increased kidney-to-body weight ratio, which was not altered by any treatment. DM increased renal inflammatory and oxidant markers, including C-reactive Protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and thiobarbituric acid reactive substances (TBARS) without altering levels of endothelin-1, Monocyte chemoattractant protein-1 (MCP-1) and glutathione peroxidase (GPx). Liraglutide normalized levels of CRP and TNF-α, though adding dapagliflozin provided no additional improvement. None of the treatments changed renal levels of IL-6, TBARS, and GPx levels, however, all reduced nitric oxide. DM increased renal fibrosis. Liraglutide, but not dapagliflozin, normalized renal fibrosis, tumor growth factor-β, and collagen type IV. CONCLUSION: Liraglutide, but not dapagliflozin, attenuated renal inflammation and fibrosis, supporting its use in preventing diabetic kidney injury.