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Abstract
Background: Hypertension is one of the major risk factors for developing end stage renal failure. The oxidative stress has a fundamental role in deleterious structural and functional renal changes in hypertensive rats. Several experimental studies have suggested that dipeptidyl peptidase IV (DPP-IV) inhibitors ameliorate diabetic renal injury and improve renal oxidative stress. Aim: The present study was undertaken to assess the possible protective effects of sitagliptin, a DPP-IV inhibitor, alone and its combination with either losartan or amlodipine against N}-nitro-L-arginine methyl ester (L-NAME) induced hypertensive nephropathy in rats. Results: chronic L-NAME administration resulted in significant elevation in the body weight and mean arterial pressure. When compared with the control group; urine volume, urine creatinine, creatinine clearance, kidneys` weight and kidney/body weight percentage were significantly decreased, while, serum urea, serum creatinine, albuminuria, albumin creatinine ratio, plasma SDF-1Ü and renal tissue MDA content were significantly elevated. Histopathological changes in the rats` kidneys were observed in the form of congested glomeruli, loss of Bowman`s space, capillary congestion and haemorrhage, in addition to dense collagen fibers deposition in adventitia. Treatment with sitagliptin successfully ameliorated the deleterious effects of L-NAME on all tested parameters. And this effect was enhanced by adding sitagliptin to anti-hypertensive drugs either losartan or amlodipine. Conclusion: sitagliptin attenuated hypertensive nephropathy induced by chronic administration of L-NAME in rats. An effect which is mediated through increase in plasma SDF-1 Ü level and decrease lipid perodixation indicated by reduction of renal MDA level. This protective effect was enhanced by adding sitagliptin to the anti- hypertensive drugs losartan or amlodipine.