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Type: Artigo de periódico
Title: Hepatic gene expression profile associated with non-alcoholic steatohepatitis protection by S-nitroso-N-acetylcysteine in ob/ob mice
Author: de Oliveira, CPMS
Stefano, JT
de Lima, VMR
de Sa, SV
Simplicio, FI
de Mello, ES
Correa-Giannella, ML
Alves, VAF
Laurindo, FRM
de Oliveira, MG
Giannella, D
Carrilho, FJ
Abstract: Background/Aims: To understand the molecular mechanisms underlying non-alcoholic steatohepatitis (NASH) prevention by S-nitroso-N-acetylcysteine (SNAC), an NO donor that inhibits lipid peroxidation, we examined hepatic differentially expressed genes between ob/ob mice receiving or not SNAC treatment concomitantly with a methionine-choline deficient (MCD) diet. Methods: Ob/ob mice were assigned to receive oral SNAC fed solution (MCD+SNAC group) or vehicle (MCD group) by gavage. After four weeks, histopathological analysis and microarray hybridizations were conducted in liver tissues from groups. GeneSifter (R) system was used to identify differentially expressed genes and pathways according to Gene Ontology. Results: NASH was absent in the MCD+SNAC group and no significant changes in food intake or body weight were observed in comparison to MCD group. After SNAC treatment, several genes belonging to oxidative phosphorylation, fatty acid biosynthesis, fatty acid metabolism and glutathione metabolism pathways were down-regulated in comparison to the MCD group. Conclusions: SNAC treatment promotes down regulation of several genes from fatty acid (FA) metabolism related pathways, possibly through abrogation of the cytotoxic effects of reactive oxygen species and lipid peroxides with consequent prevention of mitochondrial overload. Further studies are required to investigate the clinical implications of these findings, in attempt to develop novel therapeutic strategies for NAFLD treatment. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Subject: nitric oxide
hepatic gene expression
non-alcoholic steatohepatitis
Country: Holanda
Editor: Elsevier Science Bv
Citation: Journal Of Hepatology. Elsevier Science Bv, v. 45, n. 5, n. 725, n. 733, 2006.
Rights: fechado
Identifier DOI: 10.1016/j.jhep.2006.05.017
Date Issue: 2006
Appears in Collections:Unicamp - Artigos e Outros Documentos

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