Renoprotective Effects of Metformin and Irbesartan on Strepotozotocin-Induced Diabetic Nephropathy in Rats

Background and Aim: Diabetic Nephropathy (DN) is one of the major microvascular complication of T2DM and is the major cause of End-Stage Renal Disease (ESRD) worldwide and causes premature death in diabetic patients. It is found that between 20 to 40% of all diabetic patients are prone to developing renal failure. Angiotensin II plays a potent role in the initiation and progression of diabetic nephropathy by sustaining cell growth, inflammation and fibrosis. This study was designed to evaluate the reno protective effects of metformin and irbesartan alone and in combination on strepotozotcin-induced diabetic nephropathy in rats. Material and Methods: Diabetic nephropathy was induced in rats by Streptozotocin (STZ) 65mg/Kg/single I.P administration 15min after I.P administration of Nicotinamide (NA) (110mg/kg). Diabetic nephropathy rats were randomly divided into 4 groups. Diabetic nephropathy group, metformin treated group (100mg/kg/day), irbesartan treated group (20mg/kg/day) and (metformin + irbesartan) treated group each drug was given orally for 8 weeks 72h after STZ injection. Fasting Blood Glucose (FBG), Advanced Glycation End Products (AGEPs), blood urea, serum creatinine, urine protein, tissue Malondyaldehyde (MDA) and tissue Reduced Glutathione (RG) were measured by colorimetric methods. Renal tissue specimens were histopathologically examined by hematoxylin and eosin staining (H E). Results: Both drugs significantly reduced AGEPs, blood urea, serum creatinine, urine protein and MDA and significantly elevated RG, these results were confirmed with histopahtologcal examination with more significant effect of combination therapy over the effect of each drug alone. Conclusion: STZ induced diabetic nephropathy could be prevented with either metfromin or irbesartan by improving oxidative stress and kidney function with more significant effect of combined therapy over the effect of each drug alone.