Ethanol Acutely Impairs the Renal Conservation of 5‐Methyltetrahydrofolate in the Isolated Perfused Rat Kidney

Abstract

The ethanol-induced increase in urinary folate excretion has been shown to decrease plasma folate levels and may contribute to the development of folate deficiency associated with alcoholism. The mechanism for this effect remains to be elucidated. The present studies were designed to examine the direct effect of ethanol on the renal handling of 5-methyltetrahydrofolate (5-CH3-H4PteGlu), the physiological folate. Rats were given four consecutive hourly doses of ethanol (1 g/kg) or isocaloric doses of glucose solution orally. This treatment generated an average plasma ethanol level of 305 mg/dl. Kidneys from male Sprague-Dawley rats were removed 5 hr after initial treatment and perfused in vitro to eliminate any extrarenal effects that could confound interpretation of results. Ethanol was not added to the perfusate. These treatments had no effect on 5-CH3-H4PteGlu conservation by the isolated perfused rat kidney in comparison to experiments in which the animal received no treatment. Ethanol was then added directly to the perfusate to generate average concentrations of 293 mg/dl. The in vitro addition of ethanol significantly decreased the percentage reabsorption and increased the fractional excretion of 5-CH3-H4PteGlu in comparison to controls (kidneys perfused with or without an isocaloric dose of glucose). This effect did not become significant until the renal tissue was exposed to these levels of ethanol for 1 hr. These results indicate that ethanol directly impairs the renal conservation of 5-CH3-H4PteGlu.

Periconceptional maternal alcohol consumption and neural tube defects

“…A potential association between alcohol consumption and NTDs was first described in a case series more than 25 years ago (Friedman, 1982); however, the biological mechanisms by which alcohol impacts neural tube development are not well understood. Animal models suggest that prenatal alcohol exposure in early development can lead to excessive neural crest cell death (Bannigan and Burke, 1982), as well as contribute to folic acid deficiency via increased excretion of folic acid by the kidneys (McMartin, 1984; Muldoon and McMartin, 1994). …”

Effect of folic acid in prenatal alcohol induced behavioral impairments in Swiss albino mice

“…20–23 In vivo and in vitro studies have suggested that alcohol may impair transport of folic acid across placenta by decreasing expression of folate transport proteins. 40–42 It has been postulated that behavioral impairments associated with lower folate status are the neurodevelopmental consequences of alcohol exposure during pregnancy.…”

“…Ethanol ingestion induces a marked increase in urinary excretion of folic acid and decreases hepatic and serum folic acid, resulting into folic acid deficiency. 20–23 Gestational folic acid deficiency leads to impressive net reduction of cells in fetal brain and spinal cord. 24 It can cause a wide array of disorders in the fetal brain ranging from subtle changes in intelligence to profound mental retardation manifesting as severe damage in learning capabilities or impaired adaptation abilities in their environments.…”

Hyperhomocysteinemia and Alcoholism: A Double Hit?

“…29 Ethanol impaired the renal conservation of 5-methyltetrahydrofolate in the isolated perfused rat kidney. 30 Chronic alcoholism is known to interfere with one-carbon metabolism, for which folate, vitamin B-12, and vitamin B-6 serve as coenzymes. 31 Mean serum HCY was twice as high in chronic alcoholics compared to that of non-drinkers.…”