BACKGROUND/AIMS: 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.
BACKGROUND/AIMS: 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.
Authors: Samer Gawrieh; Tesfaye M Baye; Melanie Carless; James Wallace; Richard Komorowski; David E Kleiner; Deborah Andris; Bassem Makladi; Regina Cole; Michael Charlton; Joanne Curran; Thomas D Dyer; Jac Charlesworth; Russell Wilke; John Blangero; Ahmed H Kissebah; Michael Olivier Journal: Obes Surg Date: 2010-12 Impact factor: 4.129
Authors: Milena N Stanković; Dušan Mladenović; Milica Ninković; Ivana Ethuričić; Slađana Sobajić; Bojan Jorgačević; Silvio de Luka; Rada Jesic Vukicevic; Tatjana S Radosavljević Journal: J Med Food Date: 2013-12-10 Impact factor: 2.786
Authors: Maren C Podszun; Joon-Yong Chung; Kris Ylaya; David E Kleiner; Stephen M Hewitt; Yaron Rotman Journal: J Histochem Cytochem Date: 2020-09 Impact factor: 2.479
Authors: Carrie E McCurdy; Jacalyn M Bishop; Sarah M Williams; Bernadette E Grayson; M Susan Smith; Jacob E Friedman; Kevin L Grove Journal: J Clin Invest Date: 2009-01-19 Impact factor: 14.808