title: Sildenafil obviates ischemia-reperfusion injury-induced acute kidney injury through peroxisome proliferator-activated receptor γ agonism in rats.
abstract: BACKGROUND
  Sildenafil is a phosphodiesterase inhibitor used clinically for treating erectile dysfunction. Few studies suggest sildenafil to be a renoprotective agent. The present study investigated the involvement of peroxisome proliferator-activated receptor γ (PPAR-γ) in sildenafil-mediated protection against ischemia-reperfusion-induced acute kidney injury (AKI) in rats.
  
  
  METHODS
  The rats were subjected to ischemia-reperfusion injury (IRI) with 40 min of bilateral renal ischemia followed by reperfusion for 24 h. The renal damage was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, electrolytes, and microproteinuria in rats. The thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. The hematoxylin-eosin staining was carried out to demonstrate histopathologic changes in renal tissues. Sildenafil (0.5 and 1.0 mg/kg, intraperitoneal) was administered 1 h before subjecting the rats to renal IRI. In a separate group, bisphenol A diglycidyl ether (30 mg/kg, intraperitoneal), a PPAR-γ receptor antagonist, was given before sildenafil administration followed by IRI.
  
  
  RESULTS
  The ischemia-reperfusion demonstrated marked AKI with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. The administration of sildenafil demonstrated significant protection against ischemia-reperfusion-induced AKI. The prior treatment with bisphenol A diglycidyl ether abolished sildenafil-mediated renal protection, thereby confirming involvement of PPAR-γ agonism in the sildenafil-mediated renoprotective effect.
  
  
  CONCLUSIONS
  It is concluded that sildenafil protects against ischemia-reperfusion-induced AKI through PPAR-γ agonism in rats.
authors: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.
authors: Vinita
authors: V
authors: Mohey
authors: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.
authors: Manjinder
authors: M
authors: Singh
authors: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.
authors: Nikkita
authors: N
authors: Puri
authors: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India; Department of Pharmacology, Khalsa College of Pharmacy, Amritsar, India.
authors: Tajpreet
authors: T
authors: Kaur
authors: Department of Veterinary Anatomy, Guru Angad Dev Veterinary and Animal Science University, Ludhiana, India.
authors: Devendra
authors: D
authors: Pathak
authors: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India. Electronic address: apsingh82@gmail.com.
authors: Amrit Pal
authors: AP
authors: Singh
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001559:Benzhydryl Compounds; D004353:Drug Evaluation, Preclinical; D004852:Epoxy Compounds; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D018384:Oxidative Stress; D047495:PPAR gamma / Q000819:agonists*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011507:Proteinuria / Q000517:prevention & control; D011897:Random Allocation; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D000068677:Sildenafil Citrate / Q000494:pharmacology / Q000627:therapeutic use*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004852:Epoxy Compounds; D047495:PPAR gamma; D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds
keywords: Ischemia; Kidney; Oxidative stress; PPAR-γ; Phosphodiesterase; Sildenafil