S Väkeväinen1, J Tillonen, M Salaspuro. 1. Research Unit of Alcohol Diseases, Helsinki University Central Hospital, Helsinki, Finland.
Abstract
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.
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: Yuki Matsumura; Na Li; Hanan Alwaseem; Odelya E Pagovich; Ronald G Crystal; Matthew B Greenblatt; Katie M Stiles Journal: Hum Gene Ther Date: 2020-01-28 Impact factor: 5.695
Authors: J P Visapää; K Götte; M Benesova; J Li; N Homann; C Conradt; H Inoue; M Tisch; K Hörrmann; S Väkeväinen; M Salaspuro; H K Seitz Journal: Gut Date: 2004-06 Impact factor: 23.059