Effects of acute ethanol on urinary excretion of 5-methyltetrahydrofolic acid and folate derivatives in the rat

Acute ethanol treatment enhances the urinary excretion of endogenous folate. This effect has been implicated in the development of folate deficiency associated with chronic alcoholism. Previous studies have shown that urinary excretion of total [3H]-label after administration of [3H]folic acid is slightly higher in ethanol-treated rats because of conversion of the tracer to forms whose excretion is not affected by ethanol. Since [3H]folic acid is not the physiological substrate for the kidney, studies were performed using a high specific activity 5-methyltetrahydrofolic acid ([3H]5-CH3-H4 folic acid). Male Sprague-Dawley rats were given four consecutive hourly doses of ethanol at 1 g/kg, followed by infusion of [3H]5-CH3-H4 folic acid at 5 h. Urine samples were collected to 6 h, when rats were killed, and plasma, liver and kidney samples were collected. Endogenous urinary folate excretion and the fractional urinary excretion of both endogenous and [3H]5-CH3-H4 folic acid at the 5-6 h time period were significantly higher in ethanol-treated rats. The kidney had a tenfold greater specific incorporation of [3H]-label than did the liver. High performance liquid chromatography (HPLC) analysis of the plasma obtained at 6 h showed that 68% of the label was [3H]5-CH3-H4 folic acid, and HPLC analysis of the urine obtained from 5-6 h showed that only 10% of the label was [3H]5-CH3-H4 folic acid. The data indicate that [3H]5-CH3-H4 folic acid was rapidly taken up by the kidney and metabolized to other folate and nonfolate forms, which were then secreted into the renal tubule for excretion.(ABSTRACT TRUNCATED AT 250 WORDS)