Diabetic nephropathy becomes the single most frequent cause of end-stage renal disease. The present study aimed therefore to investigate possible protective effect of eprosartan, an angiotensin II type 1 receptor blocker, on high-fat diet/streptozotocin-induced early diabetic nephropathy in rats and various mechanisms underlie this effect. Male Wistar rats with type 2 diabetes induced by high-fat diet/streptozotocin were treated with eprosartan at the dose levels of 30 and 60mg/kg daily for 5 weeks. Eprosartan induced a nephroprotective effect as evident by the significant decrease in serum creatinine, urea, total cholesterol, triglycerides and glucose levels, urinary albumin excretion and kidney index as well as renal levels of malondialdehyde and nitric oxide products (nitrite/nitrate), in addition to angiotensin II, inducible nitric oxide synthase, transforming growth factor-β1 and collagen IV expressions with a concurrent increase in renal levels of reduced glutathione and catalase activity compared to diabetic untreated rats. Histopathological examination confirmed the renoprotective effect of eprosartan. In conclusion, eprosartan protects rats against high-fat diet/streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant effect as well as by abrogating the overexpression of angiotensin II, inducible nitric oxide synthase, transforming growth factor-β1 and collagen IV.
Keywords: Angiotensin II; Collagen IV; Diabetic nephropathy; Eprosartan; Inducible nitric oxide synthase; Transforming growth factor-β(1).
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