- 作者：Claudia Pinto Marques Souza de Oliveira ; José ; Tadeu Stefano ; Vicê ; ncia Mara Rodrigues de Lima ; Sandra Valé ; ria de Sá ; Fernanda Ibanez Simplicio ; Evandro Sobrosa de Mello ; Maria L
- 刊名：Journal of Hepatology
- 出版年：2006
- 出版时间：November 2006
- 年：2006
- 卷：45
- 期：5
- 页码：725-733
- 全文大小：301 K
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® 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.