Antioxidant preserving effects of Emphasis Type="

Authors: Arash Bidadkosh Amin Derakhshanfar Amir Mahmoud Rastegar Saleh Yazdani

Publish Date: 2011/11/11

Volume: 21, Issue: 6, Pages: 1739-1744

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Abstract

Nephrotoxicity results from an abrupt decline in glomerular functions of the kidney and is regarded as a major cause of concern for limiting therapeutic uses of gentamicin in hospital settings Recent evidences suggest that both endothelial nitric oxide synthesis eNOS and inducible NOS iNOSderived nitric oxide NO vasodilators reduce renal toxicity restoring normal glomerular functions and hemodynamic stability but this has not been adequately investigated in gentamicin nephrotoxicity To determine the isoform of NOS that plays a predominant role in the control of glomerular vasodilation under the oxidative stress of nephrotoxicity we conducted a controlled randomized study in five equal groups of ten Sprague–Dawley rats All animals were given a corresponding dose of either normal saline only larginine only gentamicin or a combination thereof with and without N3aminomethyl benzylacetamidine a selective iNOS inhibitor 1400W for 9 days After 6 days gentamicintreated rats developed nephrotoxic alterations evident by a significant fall in renal blood flow and glomerular filtration rate increased urinary excretion of gamma glutamyl transpeptidase and serum concentration of inflammatory interleukins IL6 and IL8 as well as a decrease in the tissue antioxidant activity of superoxide dismutase Changes in these biochemical variables were completely inhibited by supplemented larginine up to 9 days However a combination of 1400W partially removed protective effects of larginine on the glomerular hemodynamics of the kidney Our results suggest that at irradiation of eNOS developed by increased oxidative process administration of larginine increases iNOSderived NO production and glomeruli infiltration on its direct antioxidant effects counteracting the undesirable effects of peroxynitrite formation on the kidneyThe authors are grateful to the Shiraz University staff and would like to thank Dr A Monabbati Department of Pathology for his technical assistance in the reviewing of slides and Prof A Zakeri Department of Physics for his kind cooperation in statistical analysis of data

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