title: Oxidative stress in the pathogenesis of nonalcoholic fatty liver disease, in rats fed with a choline-deficient diet.
abstract: OBJECTIVE
  The pathogenesis of Nonalcoholic Fatty Liver Disease remains largely unknown, but oxidative stress seems to be involved. The aim of this study was to evaluate the role of oxidative stress in experimental hepatic steatosis induced by a choline-deficient diet.
  
  
  METHODS
  Fatty liver disease was induced in Wistar rats by a choline-deficient diet. The animals were randomized into three groups: I (G1) and II (G2), n=6 each--fed with a choline-deficient diet for four and twelve weeks respectively; Group III (control-G3; n=6)--fed with a standard diet for twelve weeks. Samples of plasma and liver were submitted to biochemical, histological and oxidative stress analysis. Variables measured included serum levels of aminotransferases (AST, ALT), cholesterol and triglycerides. Oxidative stress was measured by lucigenin-enhanced luminescence and the concentration of hydroperoxides (CE-OOH-cholesteryl ester) in the liver tissue.
  
  
  RESULTS
  We observed moderate macro- and microvesicular fatty change in periportal zones G1 and G2 as compared to controls (G3). In G2, fatty change was more severe. The inflammatory infiltrate was scanty and no fibrosis was seen in any group. There was a significant increase of AST and triglycerides in G1 and G2 as compared to control group G3. The lucigenin-amplified luminescence (cpm/mg/min x 10(3)) was significantly increased in G1 (1393-/+790) and G2 (7191-/+500) as compared to controls (513-/+170), p<0.05. The concentrations of CE-OOH were higher in G1 (5.7-/+0.9 nmol/mg protein) as compared to control (2.6-/+0.7 nmol/mg protein), p<0.05.
  
  
  CONCLUSIONS
  1) Oxidative stress was found to be increased in experimental liver steatosis; 2) The production of reactive oxygen species was accentuated when liver steatosis was more severe; 3) The alterations produced by oxidative stress could be an important step in the pathogenesis of nonalcoholic fatty liver disease.
authors.affiliation: Deptartment of Gastroenterology of the Medical School, University of São Paulo, Instituto Central, São Paulo, Brazil. mauclaud@uol.com.br
authors.forename: Claudia P M S
authors.initials: CP
authors.lastname: Oliveira
authors.forename: L Carlos
authors.initials: LC
authors.lastname: da Costa Gayotto
authors.forename: Caroline
authors.initials: C
authors.lastname: Tatai
authors.forename: Bianca Ishimoto
authors.initials: BI
authors.lastname: Della Bina
authors.forename: M
authors.initials: M
authors.lastname: Janiszewski
authors.forename: E S
authors.initials: ES
authors.lastname: Lima
authors.forename: Dulcinéia S P
authors.initials: DS
authors.lastname: Abdalla
authors.forename: F P
authors.initials: FP
authors.lastname: Lopasso
authors.forename: F R M
authors.initials: FR
authors.lastname: Laurindo
authors.forename: A A
authors.initials: AA
authors.lastname: Laudanna
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D002794:Choline / Q000008:administration & dosage*; D002796:Choline Deficiency / Q000503:physiopathology*; D004032:Diet; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D014280:Triglycerides; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002794:Choline