title: Nrf2 activation protects the liver from ischemia/reperfusion injury in mice.
abstract: OBJECTIVE
  To investigate the role of Nrf2 in the pathogenesis of hepatic ischemia-reperfusion (I/R) injury.
  
  
  BACKGROUND
  Hepatic I/R injury is a serious complication that leads to liver failure after liver surgery. NF-E2-related factor 2 (Nrf2) is a transcription factor that plays a critical role in protecting cells against oxidative stress. Therefore, it is suggested that Nrf2 activation protects the liver from I/R injury.
  
  
  METHODS
  Wild-type and Nrf2-deficient mice were treated with 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2), or a vehicle. Subsequently, these mice were subjected to 60-minute hepatic 70% ischemia, followed by reperfusion. Liver and blood samples were collected to evaluate liver injury and mRNA expressions.
  
  
  RESULTS
  After hepatic I/R, Nrf2-deficient livers exhibited enhanced tissue damage; impaired GSTm1, NQO1, and GCLc inductions; disturbed redox state; and aggravated tumor necrosis factor α mRNA expression in comparison with wild-type livers. 15d-PGJ2 treatment protected the livers of wild-type mice from I/R injury via increased expressions of GSTm1, NQO1, and GCLc; maintained redox status; and decreased tumor necrosis factor α induction. These effects induced by 15d-PGJ2 were not seen in the livers of Nrf2(-/-) mice and were not annulled by peroxisome proliferator-activated receptor γ antagonist in Nrf2(+/+) mice, suggesting that the protective effect of 15d-PGJ2 is mediated by Nrf2-dependent antioxidant response.
  
  
  CONCLUSIONS
  Nrf2 plays a critical role in the mechanism of hepatic I/R injury and would be a new therapeutic target for preventing hepatic I/R injury during liver surgery.
authors.affiliation: *Department of Gastroenterological Surgery, Akita University Graduate School of Medicine, Akita, Japan †Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kudoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchinami
authors.forename: Masato
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Ekihiro
authors.initials: E
authors.lastname: Seki
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008099:Liver / Q000098:blood supply*; D017093:Liver Failure / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012333:RNA, Messenger