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Cited by 50Alcohol Consumption and Health EffectsAlcoholism and Thiamine DeficiencyPrenatal Substance Exposure Effects

EVIDENCE OF ACETALDEHYDE-PROTEIN ADDUCT FORMATION IN RAT BRAIN AFTER LIFELONG CONSUMPTION OF ETHANOL

Rintala, J.·2000·Alcohol and Alcoholism
DOI 10.1093/alcalc/35.5.458
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Abstract

Acetaldehyde, the first metabolite of ethanol, has been shown to be capable of binding covalently to liver proteins in vivo, which may be responsible for a variety of toxic effects of ethanol. Acetaldehyde-protein adducts have previously been detected in the liver of patients and experimental animals with alcoholic liver disease. Although a role for acetaldehyde as a possible mediator of ethanol-induced neurotoxicity has also been previously suggested, the formation of protein-acetaldehyde adducts in brain has not been examined. This study was designed to examine the occurrence of acetaldehyde-protein adducts in rat brain after lifelong ethanol exposure. A total of 27 male rats from the alcohol-preferring (AA) and alcohol-avoiding (ANA) lines were used. Four ANA rats and five AA rats were fed 10-12% (v/v) ethanol for 21 months. Both young (n = 10) and old (n = 8) rats receiving water were used as controls. Samples from frontal cortex, cerebellum and liver were processed for immunohistochemical detection of acetaldehyde adducts. In four (two ANA, two AA rats) of the nine ethanol-exposed rats, weak or moderate positive reactions for acetaldehyde adducts could be detected both in the frontal cortex and cerebellum, whereas no such immunostaining was found in the remaining five ethanol-treated rats or in the control rats. The positive reaction was localized to the white matter and some large neurons in layers 4 and 5 of the frontal cortex, and to the molecular layer of the cerebellum. Interestingly, the strongest positive reactions were found among the ANA rats, which are known to display high acetaldehyde levels during ethanol oxidation. We suggest that acetaldehyde may be involved in ethanol-induced neurotoxicity in vivo through formation of adducts with brain proteins and macromolecules.

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  • Reactive electrophilic acetaldehyde can strongly induce covalent adduct formation with nucleophilic molecules such as proteins and DNA, forming AA-protein or AA-DNA adducts in the brain.

    “Additionally, reactive electrophilic acetaldehyde can strongly induce covalent adduct formation with nucleophilic molecules such as proteins and DNA, forming acetaldehyde-protein (AA-protein) or acetaldehyde-DNA (AA-DNA) adducts in the brain187–189.”

    From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [189]

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Authors
Rintala, J.
Affiliations
University of Tampere (FI)
Corresponding author
Rintala, J.
Venue
Alcohol and Alcoholism
Publisher
Oxford University Press (OUP)
Published
2000-09-01
Volume
35
Issue
5
Pages
458-463
ISSN
  • 0735-0414 (ISSN-L)
  • 1464-3502
DOI
10.1093/alcalc/35.5.458
OpenAlex
W2157200314
Cited by
50
References
41
Citations by year
2024: 3 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 3 · 2016: 2 · 2014: 1 · 2013: 2 · 2012: 4
FWCI
2.16
Type
journal article
Language
en
Open access
closed
Locations
  • Alcohol and Alcoholism (publishedVersion)
  • PubMed (publishedVersion)
  • STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Neurology › Alcoholism and Thiamine Deficiency
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
Keywords
ethanol neurotoxicity, chronic ethanol exposure, alcohol-preferring rats, frontal cortex, cerebellum, white matter, acetaldehyde, alcoholism
MeSH terms
Acetaldehyde, Alcohol Drinking, Ethanol, Animals, Brain, Central Nervous System Depressants, Cerebellum, Cerebral Cortex, Liver, Male, Proteins, Rats

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