Antioxidant preserving effects of l-arginine at reducing the hemodynamic toxicity of gentamicin-induced rat nephrotoxicity: pathological and biochemical findings

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 (iNOS)-derived 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 l -arginine, only gentamicin, or a combination thereof with and without N -3-aminomethyl benzylacetamidine (a selective iNOS inhibitor, 1400W) for 9 days. After 6 days, gentamicin-treated 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 (IL-6 and IL-8) as well as a decrease in the tissue antioxidant activity of superoxide dismutase. Changes in these biochemical variables were completely inhibited by supplemented l -arginine up to 9 days. However, a combination of 1400W partially removed protective effects of l -arginine on the glomerular hemodynamics of the kidney. Our results suggest that at irradiation of eNOS developed by increased oxidative process, administration of l -arginine increases iNOS-derived NO production and glomeruli infiltration on its direct antioxidant effects counteracting the undesirable effects of peroxynitrite formation on the kidney.