Abstract
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.
Highlights
Gentamicin is an effective aminoglycoside antibiotic against serious Gram-negative bacterial infections
The present study aimed to determine whether sildenafil can protect rat kidney from gentamicin-induced nephrotoxicity and to demonstrate the possible mechanisms
Histopathological examination revealed that control and sildenafil groups showed normal features of renal glomeruli and cortical tubules (Figures 1(a) and 1(b))
Summary
Gentamicin is an effective aminoglycoside antibiotic against serious Gram-negative bacterial infections. The pathogenesis of gentamicin nephrotoxicity involves multiple pathways, including oxidative stress, inflammation, reduced renal blood flow, and increased nitric oxide (NO) level [2, 3]. Sildenafil induces iNOS and eNOS expression [8]. These pharmacological multiactions offer the possibility of interacting with various pathological conditions usually through one or more of these actions. Sildenafil is being used to treat erectile dysfunction and pulmonary hypertension. It may have potential for treating several other conditions, including ischemia/reperfusion injury, myocardial infarction, heart failure, stroke, neurodegenerative diseases, and Raynaud’s phenomenon [9]. The present study aimed to determine whether sildenafil can protect rat kidney from gentamicin-induced nephrotoxicity and to demonstrate the possible mechanisms
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