Binding of acetaldehyde to rat gastric mucosa during ethanol oxidation
Autor: | Mikko Salaspuro, Risto O. Roine, Katja S. Salmela, Satu Väkeväinen, Pekka Sillanaukee, Liisa Itälä |
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Rok vydání: | 1997 |
Předmět: |
Male
Azides Radioisotope Dilution Technique Acetaldehyde Acetates Pathology and Forensic Medicine Adduct 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gastric mucosa medicine Animals Carbon Radioisotopes Rats Wistar Ethanol metabolism Sodium Azide Incubation 030304 developmental biology Fomepizole 0303 health sciences Ethanol Chromatography Alcohol Dehydrogenase Proteins General Medicine In vitro Rats Kinetics medicine.anatomical_structure chemistry Biochemistry Gastric Mucosa Pyrazoles Sodium azide 030211 gastroenterology & hepatology Protein Binding |
Zdroj: | Journal of Laboratory and Clinical Medicine. 129:627-633 |
ISSN: | 0022-2143 |
DOI: | 10.1016/s0022-2143(97)90197-9 |
Popis: | 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. |
Databáze: | OpenAIRE |
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