Role of sodium glucose cotransporter type 2 inhibitors dapagliflozin on diabetic nephropathy in rats; Inflammation, angiogenesis and apoptosis

Diabetic nephropathy is a major cause of chronic kidney disease and end-stage renal failure worldwide. Dapagliflozin Sodium-glucose co-transporter 2 (SGLT2) inhibitor is a new class of diabetic medications prescribed for the treatment of type 2 diabetes. The current study investigates the possible impact of dapagliflozin (DAPA) on inflammations, apoptosis, angiogenesis and fibrosis in early-stage diabetic nephropathy using a rat model of type 2 diabetes. Rats were divided into five groups, group1: normal vehicle group, group 2: diabetic group, group 3: diabetic+ DAPA (0.75 mg/kg), group 4: diabetic+DAPA (1.5 mg/kg), group 5: diabetic+DAPA (3 mg/kg). At the end of the study, Blood glucose level was measured. Serum insulin, BUN, and SCr were measured. Insulin resistance was determined using the homeostasis model assessment for insulin resistance (HOMA-IR) index. Renal tissue homogenization was done for assessment of inflammatory markers TNF-α, PEDF, and PTX-3, In addition to apoptosis markers BCL-2 and BAX. Histopathological examinations were done for tubular renal cells and immunohistochemical examination for fibrosis marker α-SMA and angiogenic factor VEGF. Treatments with dapagliflozin showed improvements in histopathological examinations, inflammatory and apoptotic markers compared to diabetic vehicles in a dose-dependent manner. Thus, dapagliflozin may have renoprotective effects, which be promising in diabetic patients suffered from nephropathy.