title: Involvement of peroxisome proliferator-activated receptor gamma in vitamin D-mediated protection against acute kidney injury in rats.
abstract: BACKGROUND
  Vitamin D has been reported as renoprotective agents in various studies. Recently, a few in vitro studies highlighted cross talk between vitamin D and peroxisome proliferator-activated receptor gamma (PPAR-γ). The present study investigated the activation of PPAR-γ as novel mechanism in vitamin D-mediated protection against ischemia reperfusion-induced acute kidney injury (AKI) in rats.
  
  
  METHODS
  The AKI was induced by clamping renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed by measuring creatinine clearance, serum urea, uric acid level, and lactate dehydrogenase activity. Moreover, serum potassium, calcium level, fractional excretion of sodium, and microproteinuria were measured in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acid-reactive substances, superoxide anion generation, reduced glutathione level, and catalase and myeloperoxidase activities. The hematoxylin-eosin staining was carried out to observe histopathologic changes in renal tissues. Vitamin D (0.25, 0.5, and 1 μg/kg) was administered for 7 d before subjecting rats to renal ischemia reperfusion injury (IRI).
  
  
  RESULTS
  The renal IRI in rats induced significant changes in serum, urinary, and oxidative stress parameters in renal tissues. Moreover, hematoxylin-eosin staining revealed marked damage produced by IRI in renal tissues. The administration of vitamin D at 0.5 μg/kg dose afforded maximum protection against renal IRI. The prior treatment with PPAR-γ antagonist bisphenol A diglycidyl ether significantly attenuated protective effect of vitamin D, thus confirming involvement of PPAR-γ in vitamin D-mediated renoprotection.
  
  
  CONCLUSIONS
  It is concluded that activation of PPAR-γ significantly contributes toward vitamin D-mediated protection against ischemia reperfusion-induced AKI.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Kapil
authors.forename: Jaswinder Pal
authors.initials: JP
authors.lastname: Singh
authors.forename: Tajpreet
authors.initials: T
authors.lastname: Kaur
authors.forename: Balbir
authors.initials: B
authors.lastname: Singh
authors.forename: Amrit Pal
authors.initials: AP
authors.lastname: Singh
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood / Q000652:urine; D004195:Disease Models, Animal; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D047495:PPAR gamma / Q000378:metabolism*; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D014508:Urea / Q000097:blood; D014527:Uric Acid / Q000097:blood; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology*; D014815:Vitamins / Q000378:metabolism / Q000494:pharmacology
chemical_list: D047495:PPAR gamma; D014815:Vitamins; D014807:Vitamin D; D014527:Uric Acid; D014508:Urea; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D011188:Potassium; D002118:Calcium
keywords: Acute kidney injury; Oxidative stress; PPAR-γ; Vitamin D