title: The effect of sildenafil on cisplatin nephrotoxicity in rats.
abstract: Sildenafil, the first drug for erectile dysfunction, has cardiopulmonary protective actions. A recent study has reported that sildenafil given intraperitoneally (i.p.) attenuated cisplatin (CP)-induced nephrotoxicity. Here, we evaluated whether sildenafil, given by two different routes and at two different doses, can attenuate CP-induced nephrotoxicity and would also affect renal haemodynamics in CP-treated rats. Six groups of rats were treated with saline (controls), CP [5 mg/kg, intraperitoneally (i.p.) once], sildenafil (0.4 mg/kg/day, i.p. for 5 days), sildenafil (0.4 mg/kg/day i.p. for 5 days) plus CP (5 mg/kg, i.p., once), sildenafil [10 mg/kg/day, subcutaneous (s.c.) for 5 days] or sildenafil (10 mg/kg/day, s.c. for 5 days) plus CP (5 mg/kg, i.p. once). Five days after the end of the treatments, urine was collected from all rats, which were then anaesthetized for blood pressure and renal blood flow monitoring. This was followed by intravenous (i.v.) injection of norepinephrine for the measurement of renal vasoconstrictor responses. Thereafter, blood and kidneys were collected for measurement of several biochemical, functional and structural parameters. CP reduced body-weight and renal blood flow but did not affect norepinephrine-induced renal vasoconstriction. It increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. CP caused extensive renal tubular necrosis, increased urine volume and N-acetyl-β-D-glucosaminidase activity. When sildenafil (0.4 mg/kg/day, i.p. for 5 days) was combined with cisplatin, there was a dramatic improvement in renal histopathology, reduction in N-acetyl-β-D-glucosaminidase and increase in renal blood flow. However, sildenafil (10 mg/kg/day, s.c. for 5 days) did not affect CP nephrotoxicity, suggesting the importance of dose and route selection of sildenafil as a nephroprotectant.
authors.affiliation: Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khod, Sultanate of Oman.
authors.forename: Badreldin H
authors.initials: BH
authors.lastname: Ali
authors.forename: Aly M
authors.initials: AM
authors.lastname: Abdelrahman
authors.forename: Suhail
authors.initials: S
authors.lastname: Al-Salam
authors.forename: Munjusha
authors.initials: M
authors.lastname: Sudhadevi
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: AlMahruqi
authors.forename: Ishaq S
authors.initials: IS
authors.lastname: Al-Husseni
authors.forename: Sumiya
authors.initials: S
authors.lastname: Beegam
authors.forename: Subramanian
authors.initials: S
authors.lastname: Dhanasekaran
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Nemmar
authors.forename: Mansour
authors.initials: M
authors.lastname: Al-Moundhri
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D007279:Injections, Subcutaneous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D009336:Necrosis / Q000139:chemically induced; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D002945:Cisplatin