ALCOHOL-INDUCED LIVER DAMAGE: ROLE OF XANTHINE OXIDASE

Project Details

Description

The long term objective of this project is to supply information which will
aid in the development of strategies for treatment and/or prophylaxis of
ethanol-induced hepatotoxicity. It seeks to accomplish this objective by
investigating a potential mechanism through which ethanol might exert its
hepatotoxic effects. This research will focus on the elucidation of the
effects of acute and chronic ethanol treatment on the hepatic xanthine
dehydrogenase/oxidase system in rats. Both the potential conversion of
xanthine dehydrogenase to the oxidase form of the enzyme and the
accumulation of the substrate hypoxanthine as a result of ethanol-induced
liver hypoxia could contribute markedly to liver damage through production
of the highly toxic superoxide anion radical. If so, inhibition of
xanthine oxidase by the drug allopurinol might diminish the hepatotoxic
effects of ethanol. The specific aims of this proposal are as follows:
1. To determine if acute or chronic ethanol treatment causes the conversion
of xanthine dehydrogenase to xanthine oxidase, as well as the accumulation
of hypoxanthine in vivo, thereby triggering the production of the highly
toxic superoxide anion radical. 2. To determine if effects of ethanol
treatment on the hepatic xanthine dehydrogenase/oxidase system are
responsible for the predisposition of ethanol treated animals to liver
damage resulting from hypoxia. 3. To determine if inhibition of xanthine
oxidase by the drug allopurinol can diminish ethanol-induced hepatotoxicity
in rats subjected to brief hypoxia.
StatusFinished
Effective start/end date8/1/867/31/88

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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