| [ Summary ] |
Oxidative stress may play an important role in the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Oxidative stress is generated through multiple sources, including oxidation of free fatty acids, cytochrome P450 2E1, iron overload, and hepatic necro-inflammation caused by endotoxin and proinflammatory cytokines. Oxidative stress may trigger damage to cellular membranes and DNA, which results in lipid peroxidation and oxidative DNA damage, respectively. Our immunohistochemical study revealed that 4-hydroxy-2'-nonenal (HNE), as a reliable marker of lipid peroxidation, was frequently detected in livers with non-alcoholic fatty liver disease. In NASH, the labeling index for HNE was significantly correlated with the grade of necro-inflammation, as well as the stage of fibrosis. Hepatic expression of 8-hydroxydeoxyguanosine (8-OHdG), a good biomarker of oxidative DNA damage, was preferentially detected in livers with NASH. Interestingly, there was a significant correlation between the 8-OHdG index and the grade of necro-inflammation. These observations suggest that oxidative stress-induced cellular injury occurs widely in livers with NASH and may be associated with some clinico-pathological features of NASH, including liver fibrosis and possibly, hepatocarcinogenesis. Therefore, it is conceivable that treatment of NASH to suppress oxidative stress may have clinical benefits. |