Relationship of alcohol metabolism to folate deficiency produced by ethanol in the rat.
Chronic ethanol use can lead to folic acid deficiency in humans. In rats, acute doses of ethanol produce a marked increase in urinary folate excretion, which precedes a decrease in plasma folate levels. To assess the role of ethanol and its metabolism in these effects, five groups of male Sprague-Dawley rats were treated orally as follows: (1) ethanol in 4 doses of 1 g/kg each at 0, 1, 2 and 3 hr; (2) ethanol, as above, plus the alcohol dehydrogenase inhibitor 4-methylpyrazole (4-MP) at 50 mg/kg IP 15 min prior to 0 hr; (3) glucose in 4 isocaloric doses; (4) glucose plus 4-MP as above; (5) methanol in 4 doses of 1 g/kg. Urinary folate levels (by Lactobacillus casei assay) peaked in both ethanol- and methanol-treated rats at the same time as the urine alcohol levels (6-8 hr) and then declined with a similar time course. Urinary levels of formic acid, which is eliminated by oxidation by a folate-dependent pathway, were significantly increased by ethanol administration, thus indicating another ethanol-folate interaction. Concurrent administration of 4-MP suppressed the increased excretion of formate but had no effect on the increased excretion of folate in ethanol-treated rats. These studies suggest that ethanol has two distinct effects on folate metabolism, one dependent and one independent of ethanol metabolism.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism* / Q000633:toxicity; D005492:Folic Acid / Q000652:urine; D005494:Folic Acid Deficiency / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D000432:Methanol / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D009243:NAD; D000431:Ethanol; D005492:Folic Acid; D000432:Methanol