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 e xogenous or metabolically derived-binds to gastric mucosal proteins. H omogenized rat gastric mucosa was incubated with various concentration s 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, a nd the acetaldehyde formed was measured by using headspace gas chromat ography, Incubation of gastric mucosa with (C-14)-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 mu mol/L). Stable ad ducts represented 77% +/- 5% (mean +/- SEM) of the total adducts forme d. In the presence of ethanol, acetaldehyde production and adduct form ation took place in a concentration- and time-dependent manner, 4-Meth ylpyrazole 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 clearl y reflected in increased adduct formation (550% +/- 110%). In conclusi on, both exogenous and endogenous acetaldehyde binds to gastric mucosa l proteins in vitro. Gastric mucosal acetaldehyde production and the c onsequent adduct formation could be a pathogenetic factor behind ethan ol-associated gastric injury.