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Cytoplasmic fine granular expression of 8-hydroxydeoxyguanosine reflects early mitochondrial oxidative DNA damage in nonalcoholic fatty liver disease.

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Department of Pathology, University of Toyama, 2630 Sugitani, Toyama-City, Toyama, Japan.


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.

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