Metabolism of ethanol to acetaldehyde by rat uterine horn subcellular fractions.
Controversial studies from others suggested that alcohol intake could be associated with some deleterious effects in the uterus. Not all the effects of alcohol drinking on female reproductive organs can be explained in terms of endocrine disturbances. Deleterious effect of alcohol or its metabolites in situ could also play a role. Accordingly, we found a metabolism of alcohol to acetaldehyde in the rat uterine horn tissue cytosolic fraction mediated by xanthine oxidoreductase, requiring a purine cosubstrate and inhibited by allopurinol. This activity was detected by histochemistry in the epithelium and aldehyde dehydrogenase activity was detected in the muscular layer and in the serosa. There was a microsomal process, not requiring NADPH and of enzymatic nature, oxygen-dependent and inhibited by diethyldithiocarbamate, diphenyleneiodonium and partially sensitive to esculetin and nordihydroguaiaretic acid. The presence of metabolic pathways in the uterine horn able to generate acetaldehyde, accompanied by a low capacity to destroy it through aldehyde dehydrogenase, led to acetaldehyde accumulation in the uterus during ethanol exposure. Results suggest that any acetaldehyde produced in situ or arriving to the uterine horn via blood would remain in this organ sufficiently to have the opportunity to react with critical molecules to cause deleterious effects.
Centro de Investigaciones Toxicológicas (CEITOX, CITEFA-CONICET) Juan B. de La Salle 4397, B1603ALO Villa Martelli, Argentina.
Lara R
LR
Buthet
Florencia M
FM
Bietto
José A
JA
Castro
Gerardo D
GD
Castro
D000079:Acetaldehyde / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D008099:Liver / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
D009243:NAD; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D014969:Xanthine Oxidase; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde