Can sildenafil citrate ameliorate cisplatin-induced nephrotoxicity? Crosstalk between the possible mechanisms

ABSTRACT

Nephrotoxicity is considered the most important side effect which limits cisplatin therapy in various diseases. It is might be due to oxidative stress, decreased renal blood flow and reduction in the glomerular filtration. Sildenafil citrate is used for treatment of erectile dysfunction, but its effect in ameliorating cisplatin nephrotoxicity was not yet clearly studied. So the present work aimed to evaluate the protective role of Sildenafil citrate against cisplatin-induced nephrotoxicity in adult male albino rats. 24 adult male albino rats were divided into 4 groups (6 rats each) Group I, control; Group II, sham control; Group III, Cisplatin-treated group, and Group IV, Sildenafil-and-Cisplatin-treated group. At the end of the experiment, the kidney of each animal was excised, trimmed and prepared for histological, histochemical and immunohistochemical study. Blood samples were obtained to evaluate the kidney functions. Kidney sections of Group III showed marked degenerative changes in the proximal convoluted tubules, vacuolations, exfoliation of the lining epithelium, cast formation and interstitial hemorrhagic exudate. There was marked elevation of serum creatinine and urea with significant increase in nitric oxide (NO) and decrease in glutathione reductase (GSH) concentrations in the kidney tissue and weak periodic acid Schiff (PAS) reaction. Treatment with Sildenafil citrate in Group IV offered marked improvement in the renal structure, kidney function tests and other parameters. The present study concluded that Sildenafil citrate could protect the kidney against Cisplatin-induced nephrotoxicity in adult male albino rat

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