title: Cytoplasmic fine granular expression of 8-hydroxydeoxyguanosine reflects early mitochondrial oxidative DNA damage in nonalcoholic fatty liver disease.
abstract: To clarify the possible role of oxidative stress in hepatocytes in nonalcoholic fatty liver disease, the hepatic expression of 8-hydroxydeoxyguanosine (8-OHdG), a good marker of oxidative DNA damage, was immunohistochemically investigated in nonalcoholic steatohepatitis (NASH) and steatosis. In double immunostaining, the cytoplasmic fine granular 8-OHdG expression was considered to reflect 8-OHdG-positive mitochondrial DNA affecting oxidation stress. In steatosis, 4 of 8 cases showed cytoplasmic 8-OHdG, 1 case showed nuclear 8-OHdG and 1 case showed both cytoplasmic and nuclear 8-OHdG. In contrast, 8-OHdG expression was more frequently detected in NASH (12 of 13 cases, 92%). Immunoreactivity for 8-OHdG was observed only in the cytoplasm with a fine granular pattern (1 of 13 cases, 8%), only in the nucleus (6 of 13 cases, 46%), and in both the cytoplasm and the nucleus (5 of 13 cases, 38%). Megamitochondria also exhibited 8-OHdG intensely. We indicate that 8-OHdG expression in the cytoplasm with a fine granular pattern reflects oxidative damage to the mitochondrial DNA of hepatocytes in both NASH and steatosis. We propose herein that the evaluation of cytoplasmic 8-OHdG may be a sensitive diagnostic marker of early nonalcoholic fatty liver disease events.
authors: Department of Pathology, University of Toyama, 2630 Sugitani, Toyama-City, Toyama, Japan. kazunomoto@syd.odn.ne.jp
authors: Kazuhiro
authors: K
authors: Nomoto
authors: Koichi
authors: K
authors: Tsuneyama
authors: Hiroyuki
authors: H
authors: Takahashi
authors: Yoshihiro
authors: Y
authors: Murai
authors: Yasuo
authors: Y
authors: Takano
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D003594:Cytoplasmic Granules / Q000378:metabolism; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress
chemical_list: D004272:DNA, Mitochondrial; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine