Binding of acetaldehyde to rat gastric mucosa during ethanol oxidation.
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.
Salmela
K S
KS
Research Unit of Alcohol Diseases, University of Helsinki, Finland.
Sillanaukee
P
P
Itälä
L
L
Väkeväinen
S
S
Salaspuro
M
M
Roine
R P
RP
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
D000085:Acetates; D001386:Azides; D002250:Carbon Radioisotopes; D011506:Proteins; D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D019810:Sodium Azide; D000426:Alcohol Dehydrogenase; D000079:Acetaldehyde