title: Genes of the antioxidant response undergo upregulation in a rodent model of nonalcoholic steatohepatitis.
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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lickteig
authors.forename: Craig D
authors.initials: CD
authors.lastname: Fisher
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Augustine
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Cherrington
mesh_terms: D000821:Animal Feed; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics; D002796:Choline Deficiency / Q000150:complications / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D004851:Epoxide Hydrolases / Q000235:genetics; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D008297:Male; D008715:Methionine / Q000172:deficiency; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D008715:Methionine; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D004851:Epoxide Hydrolases; D005721:Glutamate-Cysteine Ligase