Background and Aim: Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED), that lead to the pathogenesis of diabetic nephropathy (DN). Diabetic nephropathy (DN) is a main cause of end stage renal disease. This study was designed to investigate the protective effects of irbesartan (Irb) and its combination with pioglitazone (Pio) on impaired endothelial dysfunction, oxidative stress and inflammation beyond blood glucose control in streptozotocin (STZ) - induced diabetic nephropathy in rats.
Material and methods: forty eight male albino rats were divided equally and randomly into six groups. A (control non- diabetic non- treated), B (diabetic non- treated) by streptozotocin (65mg/kg) and nicotinamide (110 mg/kg) were injected intraperitoneally to induce diabetic nephropathy, C (diabetic treated with Irb (30mg/kg/daily) orally), D (diabetic treated with pio (30mg/kg/daily) orally) , E (diabetic treated with Irb and Pio in doses (30 mg/kg/day and 30 mg/kg/day) orally) ,and F (diabetic treated with Irb and Pio in doses (5mg/kg/day and 15mg/kg/day, respectively) orally for 12 weeks. Fasting blood glucose, urea, creatinine, albumin in urine levels, IL-6, nitric oxide (NO) and Malondialdehyde peroxidase (MDA) were determined in serum of the different groups at the end of the experiment, renal blood flow, aortic and renal histopathological changes were also evaluated.
Results: administration of irbesartan and pioglitazone to diabetic rats caused significant decrease in levels of urea, creatinine, albumin, serum inflammatory mediators (IL-6 and NO) and oxidative stress markers. The effects of irbesartan and/or pioglitazone were associated with improvement of renal blood flow and markedly reduced vascular and renal damage induced by diabetes. Conclusion: the results of the present study support that the combination of irbesartan to pioglitazone were better than monotherapy on endothelial dysfunction and diabetic nephropathy through inhibition of the pro-inflammatory mediators, NO bioavailability and oxidative stress which are independent of their glucose-lowering properties. And there were no significant difference between the combination of piogltazone and irbesartan in large doses and in low doses.
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