Role of ethanol metabolism in the alcohol-induced increase in urinary folate excretion in rats.
Chronic ethanol use can lead to folic acid deficiency in humans. In rats, acute doses of ethanol produce a marked increase in the urinary excretion of folate which is followed by a decrease in plasma folate levels. To assess the respective roles of ethanol and its metabolism in these effects, five groups of male Sprague-Dawley rats were treated orally as follows: (1) ethanol in four 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, i.p., 15 min prior to 0 hr; (3) glucose in four isocaloric doses; (4) glucose plus 4-MP as above; and (5) methanol in four doses of 1 g/kg. Total folate levels in the urine peaked in both ethanol- and methanol-treated rats at the same time as the urine alcohol levels (after 6-8 hr) and then declined over the same time course as the alcohol levels. Concurrent administration of 4-MP inhibited the metabolism of ethanol and maintained the increase in urinary folate excretion throughout 24 hr. Ethanol administration produced minor changes in the relative distribution of folate derivatives in the urine, and these changes were not prevented by 4-MP treatment. The urinary levels of formic acid, which is metabolized by folate-dependent processes, were increased by ethanol administration; this increase was prevented by 4-MP. These results suggest that ethanol is not unique among alcohols in increasing urinary folate excretion and that ethanol metabolism plays no role in the increased urinary folate excretion. However, ethanol metabolism contributes to a second effect of ethanol on the folate system, which leads to increased urinary levels of formic acid.
D000818:Animals; D004231:Diuresis; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D005492:Folic Acid / Q000652:urine*; D000077604:Fomepizole; D007700:Kinetics; D008297:Male; D000432:Methanol / Q000494:pharmacology / Q000652:urine; D011720:Pyrazoles / Q000494:pharmacology / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D005492:Folic Acid; D000432:Methanol