Increased plasma fatty acid ethyl ester levels following inhibition of oxidative metabolism of ethanol by 4-methylpyrazole treatment in human subjects

Catherine A. Best, Taisto Sarkola, C. J. Peter Eriksson, Joanne E. Cluette-Brown, Michael Laposata

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative metabolites of ethanol, mediate ethanol-induced organ damage. A direct association between pancreas-specific toxicity and increased levels of FAEE following inhibition of the oxidative metabolism of ethanol by 4-methylpyrazole (4-MP) has previously been shown in studies with rats. Methods: We obtained plasma samples from 32 healthy human volunteers who drank ethanol following 4-MP or placebo ingestion to determine whether in vivo inhibition of oxidative metabolism of ethanol causes a shift to nonoxidative metabolism of ethanol and the subsequent production of increased levels of FAEE. Plasma FAEE were isolated by solid-phase extraction and quantified by gas chromatography-mass spectrometry (GC-MS). Results: Plasma FAEE levels in subjects receiving 4-MP treatment before ethanol consumption were elevated compared with plasma FAEE concentrations taken from control subjects who received a placebo before ethanol ingestion. Increased FAEE levels in the 4-MP treatment group occurred after peak blood ethanol, and peak FAEE levels were achieved. There was a correlation between the blood ethanol and the plasma FAEE levels, and the correlation persisted in the presence or absence of 4-MP. The peak FAEE values were greater in men than in women, with or without 4-MP treatment. Conclusions: Our results indicate that the in vivo inhibition of the oxidative metabolism of ethanol using 4-MP results in an increased circulating concentration of FAEE, products of the nonoxidative metabolism of ethanol.

Original languageEnglish (US)
Pages (from-to)1126-1131
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume30
Issue number7
DOIs
StatePublished - Jul 2006
Externally publishedYes

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Enzyme inhibition
Metabolism
Esters
Ethanol
Fatty Acids
Plasmas
Therapeutics
fomepizole
Blood
Eating
Placebos
Solid Phase Extraction
Metabolites
Gas chromatography
Gas Chromatography-Mass Spectrometry
Mass spectrometry
Toxicity
Rats
Pancreas
Healthy Volunteers

Keywords

  • 4-Methylpyrazole
  • Alcohol
  • Alcoholic Pancreatitis
  • Ethanol
  • Fatty Acid Ethyl Esters

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Increased plasma fatty acid ethyl ester levels following inhibition of oxidative metabolism of ethanol by 4-methylpyrazole treatment in human subjects. / Best, Catherine A.; Sarkola, Taisto; Peter Eriksson, C. J.; Cluette-Brown, Joanne E.; Laposata, Michael.

In: Alcoholism: Clinical and Experimental Research, Vol. 30, No. 7, 07.2006, p. 1126-1131.

Research output: Contribution to journalArticle

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abstract = "Background: Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative metabolites of ethanol, mediate ethanol-induced organ damage. A direct association between pancreas-specific toxicity and increased levels of FAEE following inhibition of the oxidative metabolism of ethanol by 4-methylpyrazole (4-MP) has previously been shown in studies with rats. Methods: We obtained plasma samples from 32 healthy human volunteers who drank ethanol following 4-MP or placebo ingestion to determine whether in vivo inhibition of oxidative metabolism of ethanol causes a shift to nonoxidative metabolism of ethanol and the subsequent production of increased levels of FAEE. Plasma FAEE were isolated by solid-phase extraction and quantified by gas chromatography-mass spectrometry (GC-MS). Results: Plasma FAEE levels in subjects receiving 4-MP treatment before ethanol consumption were elevated compared with plasma FAEE concentrations taken from control subjects who received a placebo before ethanol ingestion. Increased FAEE levels in the 4-MP treatment group occurred after peak blood ethanol, and peak FAEE levels were achieved. There was a correlation between the blood ethanol and the plasma FAEE levels, and the correlation persisted in the presence or absence of 4-MP. The peak FAEE values were greater in men than in women, with or without 4-MP treatment. Conclusions: Our results indicate that the in vivo inhibition of the oxidative metabolism of ethanol using 4-MP results in an increased circulating concentration of FAEE, products of the nonoxidative metabolism of ethanol.",
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N2 - Background: Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative metabolites of ethanol, mediate ethanol-induced organ damage. A direct association between pancreas-specific toxicity and increased levels of FAEE following inhibition of the oxidative metabolism of ethanol by 4-methylpyrazole (4-MP) has previously been shown in studies with rats. Methods: We obtained plasma samples from 32 healthy human volunteers who drank ethanol following 4-MP or placebo ingestion to determine whether in vivo inhibition of oxidative metabolism of ethanol causes a shift to nonoxidative metabolism of ethanol and the subsequent production of increased levels of FAEE. Plasma FAEE were isolated by solid-phase extraction and quantified by gas chromatography-mass spectrometry (GC-MS). Results: Plasma FAEE levels in subjects receiving 4-MP treatment before ethanol consumption were elevated compared with plasma FAEE concentrations taken from control subjects who received a placebo before ethanol ingestion. Increased FAEE levels in the 4-MP treatment group occurred after peak blood ethanol, and peak FAEE levels were achieved. There was a correlation between the blood ethanol and the plasma FAEE levels, and the correlation persisted in the presence or absence of 4-MP. The peak FAEE values were greater in men than in women, with or without 4-MP treatment. Conclusions: Our results indicate that the in vivo inhibition of the oxidative metabolism of ethanol using 4-MP results in an increased circulating concentration of FAEE, products of the nonoxidative metabolism of ethanol.

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