Elsevier

Alcohol

Volume 5, Issue 2, March–April 1988, Pages 135-140
Alcohol

Article
Lipid peroxidation as a mechanism of alcoholic liver injury: Role of iron mobilization and microsomal induction

https://doi.org/10.1016/0741-8329(88)90010-9Get rights and content

Abstract

Lipid peroxidation has been invoked as a mechanism of alcoholic liver injury but its role has been controversial and the mechanism by which it occurs is unclear. Catalytic iron is known to play an important role in cellular injury and is produced during mobilization of ferritin iron. In vivo administration of a large acute dose of ethanol (5 g/kg) which produces hepatic lipid peroxidation in chow-fed rats resulted in mobilization of non-heme iron. The generation of NADH from alcohol metabolism via ADH or superoxide from acetaldehyde-xanthine oxidase mobilized iron from horse spleen ferritin in vitro. Chronic feeding of alcohol as 36% of energy for 6 weeks does not itself produce peroxidation in the rat but potentiates acute effects of ethanol. It produced microsomal induction which enhanced iron-stimulated lipid peroxidation and increased hepatic non-heme iron. Carbon monoxide increased rather than decreased accumulation of microsomal peroxidation products in vitro suggesting that cytochrome P-450 reductase mediates peroxidation but cytochrome P-450 may metabolize products. Incubation at lowered oxygen tensions equivalent to those observed in the perivenular zone (pO2=24 mmHg) enhanced in vitro iron mobilization but decreased peroxidation. Lipid peroxidation and its stimulation by iron mobilization and microsomal induction may be an important contributory mechanism of alcohol-induced liver injury.

References (35)

  • L.A. Videla et al.

    Effect of acute ethanol intoxication on the content of reduced glutathione of the liver in relation to its lipoperoxidative capacity in the rat

    FEBS Lett

    (1980)
  • E.D. Wills

    Effects of iron overload on lipid peroxide formation and oxidative demethylation by the liver endoplasmic reticulum

    Biochem Pharmacol

    (1972)
  • I. Anundi et al.

    Glutathione depletion in isolated hepatocytes: Its relation to lipid peroxidation and cell damage

    Acta Pharmacol Toxicol

    (1979)
  • S.D. Aust

    Lipid peroxidation

  • B.R. Bacon et al.

    Hepatic lipid peroxidation in vivo in rats with chronic iron overload

    J Clin Invest

    (1983)
  • T.H. Bothwell et al.

    Storage iron

  • S.E. Bradley
  • Cited by (0)

    View full text