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.
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.
Authors: Rafael Vercelino; Irene Crespo; Gabriela F P de Souza; Maria Jose Cuevas; Marcelo G de Oliveira; Norma Possa Marroni; Javier González-Gallego; María Jesús Tuñón Journal: J Mol Med (Berl) Date: 2010-01-09 Impact factor: 4.599
Authors: Sudheer K Mantena; Adrienne L King; Kelly K Andringa; Heather B Eccleston; Shannon M Bailey Journal: Free Radic Biol Med Date: 2008-01-03 Impact factor: 7.376
Authors: Wellington Andraus; Gabriela Freitas Pereira de Souza; Marcelo Ganzarolli de Oliveira; Luciana B P Haddad; Ana Maria M Coelho; Flavio Henrique Galvão; Regina Maria Cubero Leitão; Luiz Augusto Carneiro D'Albuquerque; Marcel Cerqueira Cesar Machado Journal: Clinics (Sao Paulo) Date: 2010-07 Impact factor: 2.365
Authors: Daniel F C Mazo; Marcelo G de Oliveira; Isabel V A Pereira; Bruno Cogliati; José T Stefano; Gabriela F P de Souza; Fabíola Rabelo; Fabiana R Lima; Venâncio A Ferreira Alves; Flair J Carrilho; Claudia P M S de Oliveira Journal: Drug Des Devel Ther Date: 2013-06-28 Impact factor: 4.162