The role of acetate in alcohol-induced alterations of uterine glucose metabolism in the mouse during pregnancy.
The acute exposure of mice to ethanol during post-implantation pregnancy has been reported to cause alterations in the levels of several glycolytic intermediates in the uterus, suggesting a possible indirect mechanism of alcohol embryo-toxicity. The present study was undertaken to assess whether the ethanol metabolite, acetate is implicated in this phenomenon. Blood and uterine alcohol concentrations in day 9--pregnant Quackenbush Swiss mice were maximal 15 minutes after the intraperitoneal injection of ethanol (3.5 g/kg body weight), and fell to almost negligible levels 6 hours later. In response to this treatment, the levels of blood and uterine acetate increased, liver glycogen decreased, plasma glucose increased, and uterine glucose, glucose-6-phosphate (G-6-P), fructose-6-phosphate (F-6-P), and citrate increased. When acetate was administered to pregnant mice in amounts approximating those generated by exposure to alcohol, the levels of uterine F-6-P and citrate increased while other metabolic parameters remained unaffected. The administration of 4-methylpyrazole to mice subsequently treated with alcohol produced conditions of alcohol exposure in the absence of ethanol-derived acetate and depressed the ethanol-induced rise in uterine G-6-P and citrate. The results support the notion that acetate contributes to the alcohol-induced alterations in metabolism, at least as far as the regulation of uterine citrate and hexose monophosphates are concerned. This, together with stress responses induced by exposure to the acute dose of alcohol, may present mechanisms underlying the fetal alcohol syndrome associated in particular with "binge" drinking.
Simm
B
B
Department of Biochemistry, Newcastle Mater Misericordiae Hospital, New South Wales, Australia.
Murdoch
R N
RN
D000085:Acetates / Q000378:metabolism / Q000633:toxicity*; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002951:Citrates / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D000077604:Fomepizole; D005636:Fructosephosphates / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005958:Glucosephosphates / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D011720:Pyrazoles / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D000085:Acetates; D001786:Blood Glucose; D002951:Citrates; D005636:Fructosephosphates; D005958:Glucosephosphates; D008112:Liver Glycogen; D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D005947:Glucose