Document Detail


4-Methylpyrazole decreases salivary acetaldehyde levels in aldh2-deficient subjects but not in subjects with normal aldh2.
MedLine Citation:
PMID:  11410717     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Carcinogenic acetaldehyde is produced from ethanol locally in the upper digestive tract via alcohol dehydrogenases (ADHs) of oral microbes, mucosal cells, and salivary glands. Acetaldehyde is further oxidized into less harmful acetate mainly by the aldehyde dehydrogenase-2 (ALDH2) enzyme. ALDH2-deficiency increases salivary acetaldehyde levels and the risk for upper digestive tract cancer in heavy alcohol drinkers. 4-methylpyrazole (4-MP) is an ADH-inhibitor which could reduce the local production of acetaldehyde from ethanol in the saliva. METHODS: Five ALDH2-deficient subjects and six subjects with normal ALDH2 ingested a moderate dose of alcohol (0.4 g/kg of body weight), whereafter their salivary acetaldehyde levels, heart rate, skin temperature, and blood pressure were followed for up to four hours. Blood acetaldehyde and ethanol levels were determined at 60 min. The experiment was repeated after a week. Two hours before the second study day, the volunteers received 4-MP, 10-15 mg/kg of body weight orally. RESULTS: Total ethanol elimination rate decreased with 4-MP by 38-46% in all subjects. 4-MP also reduced blood acetaldehyde levels and suppressed the cardiocirculatory responses of the ALDH2-deficient volunteers. In addition, salivary acetaldehyde production in ALDH2-deficient subjects was significantly reduced when correlated with salivary ethanol levels. On the contrary, 4-MP did not have any effect on salivary or blood acetaldehyde levels in subjects with normal ALDH2. CONCLUSIONS: A single dose of 4-MP before ethanol ingestion reduces ethanol elimination rate, the flushing reaction, and both blood and salivary acetaldehyde levels in ALDH2-deficient subjects but not in subjects with the normal ALDH2 genotype. These results suggest that the role of oral mucosal and glandular ADHs in salivary acetaldehyde production is minimal and support earlier findings indicating that salivary acetaldehyde production is mainly of microbial origin in subjects with normal ALDH2.
Authors:
S Väkeväinen; J Tillonen; M Salaspuro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Alcoholism, clinical and experimental research     Volume:  25     ISSN:  0145-6008     ISO Abbreviation:  Alcohol. Clin. Exp. Res.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-18     Completed Date:  2001-08-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7707242     Medline TA:  Alcohol Clin Exp Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  829-34     Citation Subset:  IM    
Affiliation:
Research Unit of Alcohol Diseases, Helsinki University Central Hospital, Helsinki, Finland.
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MeSH Terms
Descriptor/Qualifier:
Acetaldehyde / analysis,  blood,  metabolism*
Adult
Aldehyde Dehydrogenase / deficiency*,  genetics,  metabolism
Blood Pressure / drug effects
Ethanol / administration & dosage*,  blood,  pharmacokinetics
Female
Heart Rate / drug effects
Humans
Kinetics
Male
Metabolic Clearance Rate
Pyrazoles / pharmacology*
Saliva / chemistry,  metabolism*
Skin Temperature / drug effects
Chemical
Reg. No./Substance:
0/Pyrazoles; 64-17-5/Ethanol; 75-07-0/Acetaldehyde; 7554-65-6/fomepizole; EC 1.2.1.3/ALDH2 protein, human; EC 1.2.1.3/Aldehyde Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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