In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases.
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.
Seki
Shuichi
S
Third Department of Internal Medicine, Osaka City University Medical School, 1-4-3, Asahimachi, Abenoku, Osaka 545-8585, Japan.
Kitada
Takuya
T
Yamada
Takao
T
Sakaguchi
Hiroki
H
Nakatani
Kazuki
K
Wakasa
Kenichi
K
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
D000447:Aldehydes; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal