Simvastatin ameliorates diabetic nephropathy by attenuating oxidative stress and apoptosis in a rat model of streptozotocin-induced type 1 diabetes

Statins are HMG-CoA reductase inhibitors with lipid-lowering effect and commonly used to reduce cardiovascular risk in diabetic patients. The present study investigates the ameliorative effect of simvastatin (SIM) on diabetic nephropathy in rats, pointing to its anti-apoptotic and anti-oxidative stress efficacies. Diabetes was induced by a single intraperitoneal injection of 55 mg/kg body weight streptozotocin (STZ) and both control and diabetic rats received 10 mg/kg SIM for 90 days. Treatment with SIM diminished the body weight loss, blood glucose and, serum creatinine, urea and uric acid in diabetic rats. SIM improved the creatinine clearance rate and urinary levels of creatinine, urea and albumin in STZ-induced rats. Lipid peroxidation and nitric oxide (NO) were significantly increased in the diabetic kidney whereas reduced glutathione, SOD and catalase were declined. Bax and caspase-3 showed a significant increase and Bcl-2 was decreased in the kidney of diabetic rats. SIM administration reduced lipid peroxidation and NO, and improved antioxidants and the expression of apoptotic markers. Diabetic rats showed increased collagen deposition in the kidney, atrophied irregular renal corpuscles with collapsed glomeruli and tubules with degenerated epithelial lining, an effect that was reversed following treatment with SIM. In conclusion, SIM can protect against diabetic nephropathy by attenuating oxidative stress and apoptosis.