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Pathological significance of oxidative cellular damage in human alcoholic liver disease

Authors


Address for correspondence: Shuichi Seki MD, Third Department of Internal Medicine, Osaka City University Medical School, 1-4-3, Asahimachi, Abeno-ku, Osaka 545–8585, Japan. e-mail: s.seki@med.osaka-cu.ac.jp

Abstract

Aims: To investigate the pathological significance of oxidative stress-induced lipid peroxidation and oxidative DNA damage in alcoholic liver disease.

Methods and results: Hepatic expression of 4-hydroxy-2′-nonenal (HNE) adducts and 8-hydroxydeoxyguanosine (8-OHdG) as reliable markers of lipid peroxidation and oxidative DNA damage, respectively, was analysed immunohistochemically and compared with histological findings in alcoholic liver disease. While no HNE adducts were observed in control livers, HNE adducts were frequently (37 of 40 cases, 92.5%) detected in alcoholic liver disease. The localization of HNE adducts was the cytoplasm of hepatocytes and sinusoidal cells in zone 3. As for 8-OHdG, 29 of 40 cases (72.5%) with alcoholic liver disease exhibited positive immunolabelling for 8-OHdG, while 8-OHdG expression was not evident in control livers. The nuclear expression of 8-OHdG was mainly detected in the hepatocytes within the areas of active inflammation. Among histological parameters, the grade of necro-inflammation activity as well as the presence of Mallory bodies were significantly associated with the expression of HNE adducts and 8-OHdG. In addition, the severity of steatosis also correlated with HNE adduct expression.

Conclusions: Lipid peroxidation and oxidative DNA damage occur widely and may be associated with certain pathological features in human alcoholic liver disease.

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