title: Binding of acetaldehyde to rat gastric mucosa during ethanol oxidation.
abstract: Acetaldehyde, the first product of ethanol metabolism, has previously been shown to form potentially harmful adducts with various proteins. The aim of this study was to investigate whether acetaldehyde--either exogenous or metabolically derived--binds to gastric mucosal proteins. Homogenized rat gastric mucosa was incubated with various concentrations of radiolabeled acetaldehyde or ethanol for different time periods. Acetaldehyde-protein adducts were determined by a liquid scintillation counter. In addition, mucosa was incubated with nonlabeled ethanol, and the acetaldehyde formed was measured by using headspace gas chromatography. Incubation of gastric mucosa with (14C)-acetaldehyde led to a concentration- and time-dependent radiolabeling of mucosal proteins. Formation of acetaldehyde adducts occurred relatively rapidly within 30 minutes and even at low acetaldehyde levels (5 micromol/L). Stable adducts represented 77% +/- 5% (mean +/- SEM) of the total adducts formed. In the presence of ethanol, acetaldehyde production and adduct formation took place in a concentration- and time-dependent manner. 4-Methylpyrazole and sodium azide inhibited acetaldehyde production to 7% +/- 1% of control and decreased the amount of acetaldehyde adducts to 55% +/- 8%. Enhanced acetaldehyde formation (to 420% +/- 50%) was clearly reflected in increased adduct formation (550% +/- 110%). In conclusion, both exogenous and endogenous acetaldehyde binds to gastric mucosal proteins in vitro. Gastric mucosal acetaldehyde production and the consequent adduct formation could be a pathogenetic factor behind ethanol-associated gastric injury.
authors.affiliation: Research Unit of Alcohol Diseases, University of Helsinki, Finland.
authors.forename: K S
authors.initials: KS
authors.lastname: Salmela
authors.forename: P
authors.initials: P
authors.lastname: Sillanaukee
authors.forename: L
authors.initials: L
authors.lastname: Itälä
authors.forename: S
authors.initials: S
authors.lastname: Väkeväinen
authors.forename: M
authors.initials: M
authors.lastname: Salaspuro
authors.forename: R P
authors.initials: RP
authors.lastname: Roine
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism*; D000085:Acetates / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D001386:Azides / Q000494:pharmacology; D002250:Carbon Radioisotopes; D000431:Ethanol / Q000378:metabolism*; D000077604:Fomepizole; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011865:Radioisotope Dilution Technique; D051381:Rats; D017208:Rats, Wistar; D019810:Sodium Azide
chemical_list: D000085:Acetates; D001386:Azides; D002250:Carbon Radioisotopes; D011506:Proteins; D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D019810:Sodium Azide; D000426:Alcohol Dehydrogenase; D000079:Acetaldehyde