Differential effects of acute ethanol on urinary excretion of folate derivatives in the rat.
The ethanol-induced increase in the urinary excretion of folate has been determined to be both a time- and dose-dependent phenomenon and it has been speculated that this loss may enhance the development of folate deficiency. However, ethanol has only a minor effect on the renal clearance of exogenously administered [3H]folic acid [3H]PteGlu) in relation to that of inulin. To clarify this variable effect of ethanol, male Sprague-Dawley rats were given four consecutive hourly doses of ethanol at 1 g/kg and placed in metabolic chambers for collection of urine. At 5 hr, [3H]PteGlu was administered and urine samples were collected for 1 hr. At 6 hr, rats were sacrificed with collection of plasma, liver and kidney samples. A significant increase in the urinary excretion of endogenous folates occurred in ethanol-treated rats at both the 4-5- and 5- to 6-hr time periods, but no significant increase in 3H-labeled derivatives was noted in ethanol-treated rats. Subsequent high pressure liquid chromatographic analysis of urine extracts showed that the predominant 3H-labeled PteGlu metabolites were [3H]-5-formimino-H4PteGlu and the formyl-tetrahydrofolates, whereas the major endogenous form was 5-CH3-H4PteGlu. Ethanol administration increased significantly the excretion of the methyl derivative, with minor effects on the other folate forms. These results suggest that there is a selective effect of ethanol on the urinary excretion of specific folate derivatives. Also, inasmuch as no 5-formimino-H4-PteGlu was detected in the plasma, the rodent kidney appears to have the capacity for uptake and metabolism of filtered PteGlu.
Eisenga
B H
BH
Department of Pharmacology, Louisiana State University Medical Center, Shreveport.
Collins
T D
TD
McMartin
K E
KE
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000494:pharmacology*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface; D014018:Tissue Distribution
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D000431:Ethanol; D007444:Inulin; D005492:Folic Acid