Potential Effect of Sitagliptin on Experimentally Induced Hypertensive Nephropathy in Albino Rats

The present study was undertaken to assess the possible protective effects of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, alone and its combination with either losartan or amlodipine against N -nitro-Larginine methyl ester (L-NAME) induced hypertensive nephropathy in rats. Hypertensive nephropathy was induced in adult rats by administration of L-NAME for 6 weeks. Rats were treated with either sitagliptin, losartan, or amlodipine in combination with L-NAME. Also, the effect of the combination of sitagliptin with either losartan or amlodipine was tested. Mean arterial pressure was measured at 2, 4 & 6 weeks of the study. Serum urea and creatinine were measured at 3 & 6 weeks of the study. At the end of the study, plasma stromal derived factor-1 (SDF-1 ) and renal malondialdehyde (MDA) levels were measured. Finally, histopathological study was done for all groups. Chronic L-NAME administration resulted in significant elevation in the mean arterial pressure, serum urea and creatinine, plasma SDF-1 and renal tissue MDA content, when compared with the control group. 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. Our study indicates a protective effect of sitagliptin against hypertensive nephropathy induced by chronic administration of L-NAME in rats. An effect which is mediated through increases in plasma SDF-1 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.