Pathogenesis of alcoholic liver disease with particular emphasis on oxidative stress

Hiromasa Ishii, Iwao Kurose, Shinzo Kato

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Oxidative stress is well recognized to be a key step in the pathogenesis of ethanol-associated liver injury. Ethanol administration induces an increase in lipid peroxidation either by enhancing the production of oxygen reactive species and/or by decreasing the level of endogenous antioxidants. Numerous experimental studies have emphasized the role of the ethanol- inducible cytochrome P450 in the microsomes and the molybdo-flavoenzyme xanthine oxidase in the cytosol. This review shows the putative role of ethanol-induced disturbances in iron metabolism in relation to iron as a pro- oxidant factor. Ethanol administration also affects the mitochondrial free radical generation. Many previous studies suggest a role for active oxygens in ethanol-induced mitochondrial dysfunction in hepatocytes. Recent studies in our laboratory in the Department of Internal Medicine, Keio University, using a confocal laser scanning microscopic system strongly suggest that active oxidants generated during ethanol metabolism produce mitochondrial membrane permeability transition in isolated and cultured hepatocytes. In addition, acetaldehyde, ethanol consumption-associated endotoxaemia and subsequent release of inflammatory mediators may cause hepatocyte injury via both oxyradical-dependent and -independent mechanisms. These cytotoxic processes may lead to lethal hepatocyte injury. Investigations further implicate the endogenous glutathione-glutathione peroxidase system and catalase as important antioxidants and cytoprotective machinery in the hepatocytes exposed to ethanol.

Original languageEnglish
Pages (from-to)S272-S282
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume12
Issue number9-10
DOIs
Publication statusPublished - 1997 Jan 1

Keywords

  • Acetaldehyde
  • Alcoholic liver disease
  • Cytokine
  • Oxidative stress

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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