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

Abstract

Background: Diabetic nephropathy is one of the complications of diabetes caused by angiopathy of capillaries in the renalglomeruli. 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. Key words: Resveratrol,Biguanides,Diabetes,Nephropathy