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Genes of the antioxidant response undergo upregulation in a rodent model of nonalcoholic steatohepatitis
Author(s) -
Lickteig Andrew J.,
Fisher Craig D.,
Augustine Lisa M.,
Cherrington Nathan J.
Publication year - 2007
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20177
Subject(s) - gclc , downregulation and upregulation , nonalcoholic fatty liver disease , antioxidant , oxidative stress , endocrinology , medicine , heme oxygenase , chemistry , fatty liver , gclm , steatohepatitis , biology , biochemistry , heme , gene , enzyme , disease
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. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:216–220, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20177