Document Detail

Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease.
MedLine Citation:
PMID:  16470305     Owner:  NLM     Status:  MEDLINE    
Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7) or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7) for 4 weeks. The control group (N = 7) was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4) and a decrease in respiratory control rate (RCR) in the CD group (S4: 32.70 +/- 3.35; RCR: 2.55 +/- 0.15 ng atoms of O2 min-1 mg protein-1) when compared to the H and control groups (S4: 23.09 +/- 1.53, 17.04 +/- 2.03, RCR: 3.15 +/- 0.15, 3.68 +/- 0.15 ng atoms of O2 min-1 mg protein-1, respectively), P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.
C P M S Oliveira; A M M Coelho; H V Barbeiro; V M R Lima; F Soriano; C Ribeiro; N A T Molan; V A F Alves; H P Souza; M C C Machado; F J Carrilho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-02-02
Journal Detail:
Title:  Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.]     Volume:  39     ISSN:  0100-879X     ISO Abbreviation:  Braz. J. Med. Biol. Res.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-10     Completed Date:  2006-10-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8112917     Medline TA:  Braz J Med Biol Res     Country:  Brazil    
Other Details:
Languages:  eng     Pagination:  189-94     Citation Subset:  IM    
Departamento de Gastroenterologia (LIM 07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
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MeSH Terms
Choline Deficiency / complications
Disease Models, Animal
Fatty Acids, Omega-3 / administration & dosage
Fatty Liver / etiology*,  metabolism
Mitochondria, Liver / metabolism,  physiology*
Mitochondrial Diseases / complications*
Oxidative Stress / physiology*
Rats, Wistar
Reactive Oxygen Species
Severity of Illness Index
Reg. No./Substance:
0/Fatty Acids, Omega-3; 0/Reactive Oxygen Species

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