Genes of the antioxidant response undergo upregulation in a rodent model of nonalcoholic steatohepatitis

Andrew J. Lickteig, Craig D. Fisher, Lisa M. Augustine, Nathan J Cherrington

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Nonalcoholic fatty liver disease encompasses a spectrum of hepatic pathologies ranging from simple fatty liver to an inflammatory state known as nonalcoholic steatohepatitis (NASH). NASH is also characterized by severe hepatic oxidative stress. The goal of this study was to determine whether genes of the antioxidant response are induced in rodent models of nonalcoholic fatty liver disease. To simulate simple fatty liver and NASH, respectively, male Sprague-Dawley rats were fed a high-fat (HF) or a methionine and choline-deficient (MCD) diet for 8 weeks. Key marker genes of the antioxidant response that are known to undergo upregulation via activation of Nuclear Factor Erythroid 2-Related Factor 2 were measured using the branched DNA signal amplification assay. Messenger RNA levels of the antioxidant response, including NAD(P)H:quinone oxidoreductase-1 (Nqo1), Glutamate cysteine ligase catalytic (Gclc), and Heme oxygenase-1 (Ho-1), were significantly induced in MCD rat liver but not in HF rat liver. Furthermore, Nqo1 protein expression and activity underwent significant upregulation in MCD rat liver but not in HF rat liver. These data strongly indicate that the pathology induced by the MCD dietary model of NASH results in upregulation of the antioxidant response in rats.

Original languageEnglish (US)
Pages (from-to)216-220
Number of pages5
JournalJournal of Biochemical and Molecular Toxicology
Volume21
Issue number4
DOIs
Publication statusPublished - 2007

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Keywords

  • Antioxidant response
  • Epoxide hydrolase (Eh)
  • NAD(P)H:quinone oxidoreductase-1 (Nqo1)
  • Nonalcoholic fatty liver disease (NAFLD)
  • Nonalcoholic steatohepatitis (NASH)
  • Nuclear factor erythroid 2-related factor 2 (Nrf2)
  • Simple fatty liver

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Toxicology
  • Health, Toxicology and Mutagenesis

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