Sildenafil attenuates renal injury in an experimental model of rat cisplatin-induced nephrotoxicity

• Published in: Toxicology (Amsterdam) 2009-03, Vol.257 (3), p.137-143
• Main Authors: Lee, Kang Wook, Jeong, Jin Young, Lim, Beom Jin, Chang, Yoon-Kyung, Lee, Sang-Ju, Na, Ki-Ryang, Shin, Young-Tai, Choi, Dae Eun
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - antagonists & inhibitors; Antineoplastic Agents - toxicity; Apoptosis; bcl-2-Associated X Protein - biosynthesis; Biological and medical sciences; Blood Urea Nitrogen; Blotting, Western; Caspase 3 - biosynthesis; Cisplatin - antagonists & inhibitors; Cisplatin - toxicity; Cisplatin-induced nephrotoxicity; Creatinine - blood; Emergency; In Situ Nick-End Labeling; Kidney - pathology; Kidney Diseases - chemically induced; Kidney Diseases - pathology; Kidney Diseases - prevention & control; Kidney Function Tests; Male; Medical sciences; Nitric Oxide Synthase Type II - biosynthesis; Nitric Oxide Synthase Type III - biosynthesis; Phosphodiesterase Inhibitors - pharmacology; Piperazines - pharmacology; Purines - pharmacology; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - genetics; Sildenafil; Sildenafil Citrate; Sulfones - pharmacology; Toxicology
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2008.12.017

Abstract Sildenafil is the first commercially available selective inhibitor of phosphodiesterase-5 (PDE5) and is widely used for the treatment of erectile dysfunction. In recent years, investigations of the role of sildenafil in cardioprotection in animal models have received considerable interest. We evaluated whether sildenafil can attenuate cisplatin-induced nephrotoxicity in a rat experimental model. Male Sprague–Dawley rats were divided into five groups: control rats, sildenafil-control rats, cisplatin-injected rats (5 mg kg−1 IP, single dose), sildenafil-treated cisplatin-injected rats (0.4 mg kg−1 , daily), and sildenafil + NG-nitro- l -arginine methyl ester hydrochloride ( l -NAME)-treated rats. The molecular, functional, and structural parameters of the kidney were measured. At 96 h after cisplatin injection, serum levels of creatinine were lower in rats treated with both sildenafil + cisplatin compared with rats treated with cisplatin alone, and renal iNOS and eNOS expression was significantly higher in sildenafil + cisplatin-treated rats compared with rats treated with cisplatin alone (all P < 0.05). Renal Bax gene and protein expression was significantly higher in cisplatin-treated rats compared with control rats, and sildenafil treatment significantly reduced the levels of Bax and increased the renal Bax/Bcl-2 ratio ( P < 0.05). Sildenafil treatment also reduced renal caspase-3 activation and TUNEL-positive apoptotic cells. These data suggest that sildenafil attenuates experimental cisplatin-induced nephrotoxicity by preventing apoptosis.