ALTERED ALCOHOL TOXICITY AND GLUTATHIONE STATUS IN AGING

Project: Research project

Project Details

Description

The deleterious effects of both acute and chronic ethanol consumption are
enhanced in aging organisms; however, little is known of the biochemical
mechanisms involved. Our previous studies have demonstrated that a
glutathione deficiency is a general phenomenon of senescent organisms and
its correction leads to increased longevity. Since glutathione is known to
protect against ethanol toxicity by detoxifying reactive products of
ethanol metabolism such as acetaldehyde, peroxides and free radicals, we
hypothesize that many of the adverse effects of ethanol are enhanced in
aging due to a relative glutathione deficiency. Further, correction of this
deficiency will also reduce the aging impairments. The objectives of this
proposed study are to test this hypothesis by elucidating the effects of
aging on specific components of ethanol metabolism as well as biochemical
and physiological responses to ethanol administration in the aging C57BL/6
mouse model. The metabolic systems selected for study include alcohol
dehydrogenase, aldehyde dehydrogenase and the microsomal ethanol-oxidizing
system. The biochemical and physiological responses to ethanol that will be
analyzed include fatty liver development, lipid peroxidation, loss of motor
activity and hypothermia. Changes observed in these parameters will be
correlated with endogenous GSH status and chronological age. Finally, once
specific aging changes have been identified, we plan to determine the
effects of altering glutathione levels in vivo on these parameters. These
results should provide important information on the effect of aging and GSH
deficiency on several important ethanol-induced physiological and
biochemical impairments as well as the major enzyme systems involved in
ethanol metabolism. Ultimately, this research should provide essential
information regarding the sensitivity of elderly individuals to alcohol and
potential mechanisms for prevention of ethanol-related morbidity and
mortality.
StatusFinished
Effective start/end date9/17/908/31/91

Funding

  • National Institute on Alcohol Abuse and Alcoholism

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