Effect of chronic alcohol ingestion on hepatic folate distribution in the rat

Nicolas Hidiroglou, Maria E. Camilo, Harriet C. Beckenhauer, Dean J. Tuma, Anthony J. Barak, Peter F. Nixon, Jacob Selhub

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The mechanism by which ethanol impairs folate metabolism remains uncertain. In the present study, we used our new technique (affinity/HPLC) for folate analysis to study the effect of chronic alcohol ingestion on the content and distribution of folates in livers. Twelve male Sprague-Dawley rats (180 g) were divided into two groups, and fed for 4 weeks with Lieber-DeCarli semi-liquid isocaloric diets, with and without 5% ethanol. Livers were extracted in boiling, pH 9.3 borate buffers containing ascorbate/dithioerythritol. Folates in the supernatant fractions were purified by affinity chromatography and analyzed using ion pair high performance liquid chromatography. The data obtained showed that hepatic folate distribution in alcohol-treated rats differed from that of control animals in two ways. Livers from the ethanol-fed rats, when compared with those from control rats, exhibited increases in the percent concentrations of methylated tetrahydrofolates (21.46 ± 2.21 vs 14.8 ± 1.23), decreases in the percent concentrations of formylated tetrahydrofolates (25.62 ± 4.02 vs 46.18 ± 2.65) and higher concentrations of unsubstituted tetrahydrofolates (52.91 ± 3.84 vs 38.88 ± 2.50). In addition, alcohol ingestion was associated with longer glutamate chains of the folate molecules, characterized by lower relative concentrations of pentaglutamyl folates (29 vs 48%), and higher relative concentrations of hexa- and heptaglutamyl folates (55 vs 46% and 15 vs 6%) when compared with controls. The data are discussed in relation to possibility that alcohol exerts its effect through: (1) inhibition of B12-dependent methyl transfer from methyltetrahydrofolate to homocysteine; (2) diversion of formylated tetrahydrofolates toward serine synthesis; and (3) interaction of acetaldehyde with tetrahydrofolates, thereby interfering with folate coenzyme metabolism.

Original languageEnglish (US)
Pages (from-to)1561-1566
Number of pages6
JournalBiochemical Pharmacology
Volume47
Issue number9
DOIs
StatePublished - Apr 29 1994

Fingerprint

Tetrahydrofolates
Folic Acid
Rats
Eating
Alcohols
Liver
Ethanol
Metabolism
Dithioerythritol
High Pressure Liquid Chromatography
Rat control
Affinity chromatography
Borates
Acetaldehyde
Coenzymes
High performance liquid chromatography
Homocysteine
Nutrition
Affinity Chromatography
Boiling liquids

Keywords

  • acetaldehyde
  • ethanol
  • folate
  • folate analysis
  • rats

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Hidiroglou, N., Camilo, M. E., Beckenhauer, H. C., Tuma, D. J., Barak, A. J., Nixon, P. F., & Selhub, J. (1994). Effect of chronic alcohol ingestion on hepatic folate distribution in the rat. Biochemical Pharmacology, 47(9), 1561-1566. https://doi.org/10.1016/0006-2952(94)90532-0

Effect of chronic alcohol ingestion on hepatic folate distribution in the rat. / Hidiroglou, Nicolas; Camilo, Maria E.; Beckenhauer, Harriet C.; Tuma, Dean J.; Barak, Anthony J.; Nixon, Peter F.; Selhub, Jacob.

In: Biochemical Pharmacology, Vol. 47, No. 9, 29.04.1994, p. 1561-1566.

Research output: Contribution to journalArticle

Hidiroglou, N, Camilo, ME, Beckenhauer, HC, Tuma, DJ, Barak, AJ, Nixon, PF & Selhub, J 1994, 'Effect of chronic alcohol ingestion on hepatic folate distribution in the rat', Biochemical Pharmacology, vol. 47, no. 9, pp. 1561-1566. https://doi.org/10.1016/0006-2952(94)90532-0
Hidiroglou N, Camilo ME, Beckenhauer HC, Tuma DJ, Barak AJ, Nixon PF et al. Effect of chronic alcohol ingestion on hepatic folate distribution in the rat. Biochemical Pharmacology. 1994 Apr 29;47(9):1561-1566. https://doi.org/10.1016/0006-2952(94)90532-0
Hidiroglou, Nicolas ; Camilo, Maria E. ; Beckenhauer, Harriet C. ; Tuma, Dean J. ; Barak, Anthony J. ; Nixon, Peter F. ; Selhub, Jacob. / Effect of chronic alcohol ingestion on hepatic folate distribution in the rat. In: Biochemical Pharmacology. 1994 ; Vol. 47, No. 9. pp. 1561-1566.
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abstract = "The mechanism by which ethanol impairs folate metabolism remains uncertain. In the present study, we used our new technique (affinity/HPLC) for folate analysis to study the effect of chronic alcohol ingestion on the content and distribution of folates in livers. Twelve male Sprague-Dawley rats (180 g) were divided into two groups, and fed for 4 weeks with Lieber-DeCarli semi-liquid isocaloric diets, with and without 5{\%} ethanol. Livers were extracted in boiling, pH 9.3 borate buffers containing ascorbate/dithioerythritol. Folates in the supernatant fractions were purified by affinity chromatography and analyzed using ion pair high performance liquid chromatography. The data obtained showed that hepatic folate distribution in alcohol-treated rats differed from that of control animals in two ways. Livers from the ethanol-fed rats, when compared with those from control rats, exhibited increases in the percent concentrations of methylated tetrahydrofolates (21.46 ± 2.21 vs 14.8 ± 1.23), decreases in the percent concentrations of formylated tetrahydrofolates (25.62 ± 4.02 vs 46.18 ± 2.65) and higher concentrations of unsubstituted tetrahydrofolates (52.91 ± 3.84 vs 38.88 ± 2.50). In addition, alcohol ingestion was associated with longer glutamate chains of the folate molecules, characterized by lower relative concentrations of pentaglutamyl folates (29 vs 48{\%}), and higher relative concentrations of hexa- and heptaglutamyl folates (55 vs 46{\%} and 15 vs 6{\%}) when compared with controls. The data are discussed in relation to possibility that alcohol exerts its effect through: (1) inhibition of B12-dependent methyl transfer from methyltetrahydrofolate to homocysteine; (2) diversion of formylated tetrahydrofolates toward serine synthesis; and (3) interaction of acetaldehyde with tetrahydrofolates, thereby interfering with folate coenzyme metabolism.",
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