title: Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: attenuation by dehydroepiandrosterone.
abstract: BACKGROUND
  The pathogenesis of ischemia/reperfusion (I/R) involves generation of reactive oxygen and nitrogen species. This in vivo study investigates the effect of dehydroepiandrosterone (DHEA), a physiologic steroid with antioxidant properties, on oxidative balance and renal dysfunctions induced by monolateral I/R.
  
  
  METHODS
  Normal and DHEA-treated rats (4 mg/day x 21 days, orally) were subjected to monolateral renal I/R (30 minutes/6 hours). The oxidative state was determined by measuring hydrogen peroxide level and activities of glutathione-peroxidase, catalase, and superoxide dismutase. Tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production and inducible nitric oxide synthase (iNOS) levels were also measured. Hydroxynonenal content was used to probe lipid peroxidation. Functional parameters determined were creatinine levels and Na/K-ATPase activity. Immunohistochemical and morphologic studies were also performed.
  
  
  RESULTS
  A markedly pro-oxidant state was evident in the kidney of rats subjected to I/R. Both hydrogen peroxide and reactive nitrogen species (nitric oxide and iNOS) increased, whereas antioxidants decreased. Oxidant species induce TNF-alpha increase, which, in turn, produces lipoperoxidative processes, as documented by the increased hydroxynonenal (HNE) level. As final result, impaired renal functionality, hydropic degeneration, and vacuolization of proximal convolute tubules were observed in kidneys of I/R rats. DHEA pretreatment improved the parameters considered.
  
  
  CONCLUSIONS
  I/R induces oxidative stress and consequently damages the proximal convolute renal tubules. Rats supplemented with DHEA and subjected to I/R had reduced pro-oxidant state, oxidative damage, and improved renal functionality, indicating an attenuation of oxidative injury and dysfunctions mediated by I/R.
authors.affiliation: Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Aragno
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Cutrin
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mastrocola
authors.forename: Maria-Giulia
authors.initials: MG
authors.lastname: Perrelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Restivo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Poli
authors.forename: Oliviero
authors.initials: O
authors.lastname: Danni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boccuzzi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000975:Antioxidants; D003687:Dehydroepiandrosterone