title: Hepatic gene expression profile associated with non-alcoholic steatohepatitis protection by S-nitroso-N-acetylcysteine in ob/ob mice.
abstract: OBJECTIVE
  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.affiliation: University of São Paulo School of Medicine, Department of Gastroenterology, São Paulo (SP), Brazil. cpm@usp.br
authors.forename: Claudia Pinto Marques Souza
authors.initials: CP
authors.lastname: de Oliveira
authors.forename: José Tadeu
authors.initials: JT
authors.lastname: Stefano
authors.forename: Vicência Mara Rodrigues
authors.initials: VM
authors.lastname: de Lima
authors.forename: Sandra Valéria
authors.initials: SV
authors.lastname: de Sá
authors.forename: Fernanda Ibanez
authors.initials: FI
authors.lastname: Simplicio
authors.forename: Evandro Sobrosa
authors.initials: ES
authors.lastname: de Mello
authors.forename: Maria Lúcia
authors.initials: ML
authors.lastname: Corrêa-Giannella
authors.forename: Venâncio Avancini Ferreira
authors.initials: VA
authors.lastname: Alves
authors.forename: Francisco Rafael Martins
authors.initials: FR
authors.lastname: Laurindo
authors.forename: Marcelo Ganzarolli
authors.initials: MG
authors.lastname: de Oliveira
authors.forename: Daniel
authors.initials: D
authors.lastname: Giannella-Neto
authors.forename: Flair José
authors.initials: FJ
authors.lastname: Carrilho
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002796:Choline Deficiency / Q000188:drug therapy; D015536:Down-Regulation; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D020869:Gene Expression Profiling / Q000379:methods; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017382:Reactive Oxygen Species; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D005227:Fatty Acids; D017382:Reactive Oxygen Species; C024940:S-nitroso-N-acetylcysteine; D000111:Acetylcysteine