title: Ethanol-induced liver injury and changes in sulfur amino acid metabolomics in glutathione peroxidase and catalase double knockout mice.
abstract: OBJECTIVE
  Oxidative stress via generation of reactive oxygen species is suggested to be the major mechanism of alcohol-induced liver injury. We investigated the effects of glutathione peroxidase-1 and catalase double deficiency (Gpx-1(-/-)/Cat(-/-)) on liver injury and changes in the sulfur amino acid metabolism induced by binge ethanol administration.
  
  
  METHODS
  Ethanol (5 g/kg) was administered orally to the wild-type and the Gpx-1(-/-)/Cat(-/-) mice every 12 h for a total of three doses. Mice were sacrificed 6 h after the final dose.
  
  
  RESULTS
  The Gpx-1/Cat deficiency alone increased malondialdehyde levels in liver significantly. Hepatic methionine adenosyltransferase (MAT) activity and S-adenosylmethionine levels were decreased, however, glutathione contents were not changed. Ethanol administration to the Gpx-1(-/-)/Cat(-/-) mice increased the elevation of serum alanine aminotransferase activity, plasma homocysteine levels, hepatic fat accumulation and lipid peroxidation compared with the wild-type animals challenged with ethanol. Also the reduction of MAT activity and S-adenosylmethionine levels was enhanced, but MATI/III expression was increased significantly.
  
  
  CONCLUSIONS
  The results indicate that Gpx-1 and Cat have critical roles in the protection of liver against binge ethanol exposure. Augmentation of ethanol-induced oxidative stress may be responsible for the impairment of the transsulfuration reactions and the aggravation of acute liver injury in the Gpx-1(-/-)/Cat(-/-) mice.
authors.affiliation: College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul 151-742, South Korea.
authors.forename: Sun J
authors.initials: SJ
authors.lastname: Kim
authors.forename: Joo W
authors.initials: JW
authors.lastname: Lee
authors.forename: Young S
authors.initials: YS
authors.lastname: Jung
authors.forename: Do Y
authors.initials: DY
authors.lastname: Kwon
authors.forename: Hee K
authors.initials: HK
authors.lastname: Park
authors.forename: Chang S
authors.initials: CS
authors.lastname: Ryu
authors.forename: Sang K
authors.initials: SK
authors.lastname: Kim
authors.forename: Goo T
authors.initials: GT
authors.lastname: Oh
authors.forename: Young C
authors.initials: YC
authors.lastname: Kim
mesh_terms: D020642:Acatalasia / Q000235:genetics / Q000378:metabolism*; D000603:Amino Acids, Sulfur / Q000378:metabolism*; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000172:deficiency* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D008297:Male; D055432:Metabolomics; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000603:Amino Acids, Sulfur; D017382:Reactive Oxygen Species; D000431:Ethanol; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D002374:Catalase; D005979:Glutathione Peroxidase; D019392:Cytochrome P-450 CYP2E1; D008716:Methionine Adenosyltransferase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse