title: Salutary effect of pre-treatment with an Nrf2 inducer on ischemia reperfusion injury in the rat liver.
abstract: BACKGROUND
  Ischemia-reperfusion injury (IRI) is a common phenomenon occurring during liver surgery, transplantation, and trauma. IRI causes oxidative stress which plays a critical role in causing organ damage. The Nrf2 is the master regulator of numerous genes, encoding antioxidant, detoxifying, and cytoprotective molecules. Nrf2 dysfunction has been implicated in the pathogenesis of several inflammatory disorders, cancer, and aging. This study was undertaken to investigate the effect of Nrf2 pathway activator (dh404) on warm liver IRI in a rodent model.
  
  
  METHODS
  Ten Sprague-Dawley rats were treated with dh404 or vehicle. Dh404 was dissolved in sesame oil and was given orally (1.5mg/kg) the night before and 5 hours before procedures. Rat livers were subjected to 60 minutes of 70% ischemia followed by 3 hours of reperfusion. Serum ALT and Malondialdehyde (MDA) were determined and liver tissue was processed for histological examination, and determination of apoptosis, myeloperoxidase (MPO) activity, ADP/ATP ratio, and expressions of Nrf2, eNOS, anti-oxidant enzymes, and inflammatory mediators.
  
  
  RESULTS
  Serum ALT and MDA levels and tissue MPO activity were significantly lower, expression of the anti-oxidant enzyme, glutamate cysteine ligase were significantly higher, whereas expression of NFkB and COX-2 was unchanged in the dh404-treated group. Although the total Suzuki histology score did not differ significantly, the extent of sinusoidal congestion, vacuolization, and apoptosis was significantly reduced in the dh404 treated compared to the untreated group (P<0.01).
  
  
  CONCLUSIONS
  Pre-treatment with dh404 resulted in partial attenuation of hepatic ischemia reperfusion injury in rats.
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Masuda
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Chie
authors.initials: C
authors.lastname: Takasu
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Shiri
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Robles
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Pham
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Aimee
authors.initials: A
authors.lastname: Le
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Vo
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Seyed H
authors.initials: SH
authors.lastname: Farzaneh
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stamos
authors.affiliation: Department of Surgery, Medicine, University of California, Irvine, CA, USA.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Ichii
keywords: Reactive Oxygen Species; bardoxolone methyl analogue; inflammation; ischemia reperfusion injury; liver; oxidative stress