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Differential effects of acute ethanol on urinary excretion of folate derivatives in the rat



Differential effects of acute ethanol on urinary excretion of folate derivatives in the rat



Journal of Pharmacology and Experimental Therapeutics 248(3): 916-922



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.

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Accession: 002072572

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PMID: 2703978



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