title: In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases.
abstract: OBJECTIVE
  Although oxidative stress is an important candidate in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), the localization and pathological significance of oxidative stress-induced cellular damage in NAFLD remains unclear.
  
  
  METHODS
  Hepatic expression of 4-hydroxy-2'-nonenal (HNE) and 8-hydroxydeoxyguanosine (8-OHdG), as reliable markers of lipid peroxidation and oxidative DNA damage, respectively, was immunohistochemically investigated in NAFLD and the results were compared with histological findings.
  
  
  RESULTS
  While no HNE adducts were observed in control livers, they were frequently detected in NAFLD. In NASH, the localization of the adducts was in the cytoplasm of sinusoidal cells and hepatocytes with a predominance in zone 3. The grade of necro-inflammation as well as the stage of fibrosis significantly correlated with the HNE index. Regarding 8-OHdG, although no 8-OHdG expression was observed in normal liver and only a few in fatty liver, 11 of 17 cases (64.7%) with NASH exhibited nuclear expression of 8-OHdG in hepatocytes and sinusoidal cells in areas of active inflammation. The 8-OHdG index significantly correlated with the grade of necro-inflammation.
  
  
  CONCLUSIONS
  Oxidative cellular damage occurs frequently in livers with NAFLD and may be associated with some clinico-pathological features of NAFLD including liver fibrosis and possibly, hepatocarcinogenesis.
authors.affiliation: Third Department of Internal Medicine, Osaka City University Medical School, 1-4-3, Asahimachi, Abenoku, Osaka 545-8585, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Seki
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitada
authors.forename: Takao
authors.initials: T
authors.lastname: Yamada
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakatani
authors.forename: Kenichi
authors.initials: K
authors.lastname: Wakasa
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000447:Aldehydes / Q000032:analysis; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
chemical_list: D000447:Aldehydes; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal