title: Mitochondrial abnormality and oxidative stress in nonalcoholic steatohepatitis.
abstract: BACKGROUND
  Oxidative stress plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Mitochondrial abnormality may be associated with the onset and progression of NASH via excessive formation of mitochondrial reactive oxygen species. This study aimed to investigate the role of mitochondrial abnormality in NASH in relation to oxidative stress.
  
  
  METHODS
  Twenty-six patients with NASH, 11 with simple steatosis, and 10 healthy volunteers underwent clinico-pathological analysis. The liver/spleen ratio, an index of the hepatic fat content, was evaluated with computed tomography. Plasma glutathione levels were measured as an antioxidative marker, and the urinary 8-isoprostane levels and 3-nitrotyrosine staining in the liver as an oxidative stress marker. Mitochondrial abnormality was estimated by serum levels of mitochondria aspartate transaminase (mAST) and the mitochondrial staining in the liver.
  
  
  RESULTS
  Urinary 8-isoprostane levels were higher in NASH than in the healthy volunteers, whereas plasma glutathione levels were similar in the 2 groups. In NASH, urinary 8-isoprostane levels positively correlated with alanine transaminase levels and negatively with the liver/spleen ratio. The 3-nitrotyrosine staining was more advanced in simple steatosis and NASH than in the normal liver, but was similar in simple steatosis and NASH. In contrast to the normal mAST levels in the healthy volunteers and simple steatosis, serum mAST levels were elevated in one-fourth of the NASH patients and positively correlated with urinary 8-isoprostane levels in NASH. Most cases of NASH showed diffuse or focal but intense mitochondrial staining in the liver in contrast to scattered staining in simple steatosis.
  
  
  CONCLUSIONS
  Our present study demonstrated that in NASH, the enhanced oxidative stress may be associated with hepatic inflammation and the degree of fat infiltration in the liver. However, simple steatosis and NASH were both exposed to oxidative stress, while NASH alone was associated with mitochondrial abnormality. These findings indicate that mitochondrial abnormality may play a role in the onset and progression of NASH in correlation with oxidative stress.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, Nara, Japan. kojima@nmu-gw.naramed-u.ac.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kojima
authors.forename: Shinya
authors.initials: S
authors.lastname: Sakurai
authors.forename: Masahito
authors.initials: M
authors.lastname: Uemura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Morimoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamagawa
mesh_terms: D000328:Adult; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001706:Biopsy; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005234:Fatty Liver / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000473:pathology / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D012016:Reference Values; D013154:Spleen / Q000000981:diagnostic imaging; D013223:Statistics as Topic; D014057:Tomography, X-Ray Computed; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C075750:8-epi-prostaglandin F2alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D015237:Dinoprost; D001219:Aspartate Aminotransferases; D005978:Glutathione