Author/Authors :
linhart, kirsten-berit university of heidelberg - centre of alcohol research, Heidelberg, Germany , linhart, kirsten-berit salem medical centre - department of medicine (gastroenterology hepatology), Heidelberg, Germany , glassen, katharina salem medical centre - department of medicine (gastroenterology hepatology), Heidelberg, Germany , glassen, katharina university of heidelberg - centre of alcohol research, Heidelberg, Germany , peccerella, teresa university of heidelberg - centre of alcohol research, Heidelberg, Germany , peccerella, teresa salem medical centre - department of medicine (gastroenterology hepatology), Heidelberg, Germany , waldherr, rüdiger university of heidelberg - centre of alcohol research, Heidelberg, Germany , waldherr, rüdiger salem medical centre - department of medicine (gastroenterology hepatology), Heidelberg, Germany , linhart, heinz university of heidelberg - centre of alcohol research, Heidelberg, germany , linhart, heinz salem medical centre - department of medicine (gastroenterology hepatology), Heidelberg, Germany , bartsch, helmut germany cancer research centre (dkfz) - division of toxicology and cancer risk factors, Heidelberg, Germany , seitz, helmut k. salem medical centre - department of medicine (gastroenterology hepatology), Heidelberg, Germany , seitz, helmut k. university of heidelberg - centre of alcohol research, Heidelberg, Germany
Abstract :
Background: Nonalcoholic fatty liver disease (NAFLD), in particular its more aggressive formnonalcoholic steatohepatitis (NASH) is increasingly observed as a cause of end stage liver disease andhepatocellular carcinoma (HCC). Reactive oxygen species (ROS) are an important factor in the pathogenesisof HCC. ROS can react with polyunsaturated fatty acids derived from membrane phospholipids resultingin the production of reactive aldehydes as lipid oxidation (LPO) byproducts, such as 4-hydroxynonenal (4HNE). 4 HNE can react with DNA to form mutagenic exocyclic etheno-DNA adducts. ROS is inducedby inflammatory processes, but also by induction of cytochrome P450 2E1 (CYP2E1), as seen with chronicalcohol consumption.Methods: Immunohistochemical detection of CYP2E1, 4 HNE and hepatic exocyclic etheno-DNA adductswas performed on liver sections from 39 patients with NFLD. Spearman rank correlation was calculated toexamine possible correlations.Results: Exocyclic etheno-DNA adducts were detected and correlated significantly with 4 HNE, but notwith CYP2E1.Conclusions: This is the first description of highly carcinogenic exocyclic etheno-DNA adducts in NAFLDpatients. We could show that exocyclic etheno-DNA adducts significantly correlated with lipid peroxidationproduct 4 HNE, but not with CYP2E1, implying that in NAFLD ROS generation with consecutive DNAdamage is rather inflammation driven through various cytokines than by induction of CYP2E1.
