Research ArticlesCytoplasmic Fine Granular Expression of 8-hydroxydeoxyguanosine Reflects Early Mitochondrial Oxidative DNA Damage in Nonalcoholic Fatty Liver DiseaseNomoto, Kazuhiro MD*; Tsuneyama, Koichi MD* †; Takahashi, Hiroyuki MD*; Murai, Yoshihiro MD*; Takano, Yasuo MD*Author Information *Department of Pathology (I) †21st Century COE Program, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama-City, Toyama, Japan This work was partially supported by the Japanese Ministry of Education, Science, Sports and Culture, Grants-in-Aid for Scientific Research nos. 16790223 and 18590324, and the 21st Century COE Program in Japan, and Uehara Memorial Foundation. Reprints: Kazuhiro Nomoto, MD, Faculty of Medicine, Department of Pathology (I), University of Toyama, 2630 Sugitani, Toyama-City, Toyama 930-0194, Japan (e-mail: email@example.com). Received for publication December 3, 2005; accepted December 11, 2006 Applied Immunohistochemistry & Molecular Morphology: January 2008 - Volume 16 - Issue 1 - p 71-75 doi: 10.1097/PAI.0b013e31803156d5 Buy Metrics 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. © 2008 Lippincott Williams & Wilkins, Inc.