Pathogenesis of alcoholic liver disease with particular emphasis on oxidative stress

Hiromasa Ishii, Iwao Kurose, Shinzo Kato

Research output: Contribution to journalArticle

110 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
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume12
Issue number9-10
Publication statusPublished - 1997

Fingerprint

Alcoholic Liver Diseases
Oxidative Stress
Ethanol
Hepatocytes
Reactive Oxygen Species
Wounds and Injuries
Iron
Antioxidants
Endotoxemia
Acetaldehyde
Xanthine Oxidase
Mitochondrial Membranes
Internal Medicine
Glutathione Peroxidase
Microsomes
Oxidants
Cytosol
Catalase
Cytochrome P-450 Enzyme System
Lipid Peroxidation

Keywords

  • Acetaldehyde
  • Alcoholic liver disease
  • Cytokine
  • Oxidative stress

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Pathogenesis of alcoholic liver disease with particular emphasis on oxidative stress. / Ishii, Hiromasa; Kurose, Iwao; Kato, Shinzo.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 12, No. 9-10, 1997.

Research output: Contribution to journalArticle

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