Ethanol-induced liver injury and changes in sulfur amino acid metabolomics in glutathione peroxidase and catalase double knockout mice

Sun J. Kim, Joo W. Lee, Young S. Jung, Do Y. Kwon, Hee K. Park, Chang S. Ryu, Sang K. Kim, Goo T. Oh, Young C. Kim

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background/Aims: 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.

Original languageEnglish
Pages (from-to)1184-1191
Number of pages8
JournalJournal of Hepatology
Volume50
Issue number6
DOIs
StatePublished - Jun 2009

Keywords

  • Catalase
  • Ethanol-induced liver injury
  • Glutathione peroxidase
  • Knockout mice
  • Oxidative stress
  • S-adenosylmethionine
  • Transsulfuration

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