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Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to eva...

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Autores principales: Morsy, Mohamed A., Ibrahim, Salwa A., Amin, Entesar F., Kamel, Maha Y., Rifaai, Rehab A., Hassan, Magdy K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121185/
https://www.ncbi.nlm.nih.gov/pubmed/25120567
http://dx.doi.org/10.1155/2014/489382
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author Morsy, Mohamed A.
Ibrahim, Salwa A.
Amin, Entesar F.
Kamel, Maha Y.
Rifaai, Rehab A.
Hassan, Magdy K.
author_facet Morsy, Mohamed A.
Ibrahim, Salwa A.
Amin, Entesar F.
Kamel, Maha Y.
Rifaai, Rehab A.
Hassan, Magdy K.
author_sort Morsy, Mohamed A.
collection PubMed
description Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.
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spelling pubmed-41211852014-08-12 Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS Morsy, Mohamed A. Ibrahim, Salwa A. Amin, Entesar F. Kamel, Maha Y. Rifaai, Rehab A. Hassan, Magdy K. J Toxicol Research Article Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production. Hindawi Publishing Corporation 2014 2014-07-10 /pmc/articles/PMC4121185/ /pubmed/25120567 http://dx.doi.org/10.1155/2014/489382 Text en Copyright © 2014 Mohamed A. Morsy et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Morsy, Mohamed A.
Ibrahim, Salwa A.
Amin, Entesar F.
Kamel, Maha Y.
Rifaai, Rehab A.
Hassan, Magdy K.
Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS
title Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS
title_full Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS
title_fullStr Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS
title_full_unstemmed Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS
title_short Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS
title_sort sildenafil ameliorates gentamicin-induced nephrotoxicity in rats: role of inos and enos
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121185/
https://www.ncbi.nlm.nih.gov/pubmed/25120567
http://dx.doi.org/10.1155/2014/489382
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