Targeting apoptosis, advanced glycation end products and transforming growth factor-β1 by biguanides and resveratrol to ameliorate experimentally-induced diabetic nephropathy

Background: Diabetic nephropathy is one of the complications of diabetes caused by angiopathy of capillaries in the renal glomeruli . Its mechanisms may include glycosylation of renal proteins, abnormal intrarenal hemodynamics and hypertension. Resveratrol is a natural compound found in grapes and red wine that offers protective effects against many cardiovascular diseases and cancer. Metformin is a biguanide that is considered as the first-line drug for treatment of type 2 diabetes . Objective: To study the effect of each of resveratrol and metformin alone and in combination on streptozotocin (STZ)- induced diabetic nephropathy. Methods: 100 male Wistar rats were divided into 5 equal groups: Control untreated group, STZ group, STZ + Metformin group, STZ + Resveratrol group, and STZ + Resveratrol + Metformin group. Kidney weight/body weight ratio, serum fasting glucose, glycosylated Hb, blood urea, serum creatinine and creatinine clearance were determined. A part of the kidney was homogenized for determination of tissue tumor necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), nitric oxide (NO), reduced glutathione (GSH), advanced glycation end products (AGEs) and caspase-3 activity. The other part was subjected to histopathological examination. Results: Both resveratrol and metformin alone and in combina - tion induced significant increase in creatinine clearance, tissue GSH and tissue caspase-3 activity with significant decrease in kidney weight/body weight ratio, serum fasting glucose, glyco - sylated Hb, blood urea, serum creatinine, tissue TNF-α, TGF-β1, NO and AGEs and alleviated the histopathological changes com - pared to the group that received STZ alone. Conclusion: Resveratrol/metformin combination had a protec - tive effect on experimentally-induced diabetic nephropathy in rats.