Increased plasma fatty acid ethyl ester levels following inhibition of oxidative metabolism of ethanol by 4-methylpyrazole treatment in human subjects
Increased plasma fatty acid ethyl ester levels following inhibition of oxidative metabolism of ethanol by 4-methylpyrazole treatment in human subjects
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DOI：
10.1111/j.1530-0277.2006.00138.x
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发表时间：
2006-07-01
影响因子：
3.2
通讯作者：
Laposata, Michael
中科院分区：
文献类型：
--
作者：
Best, Catherine A.;Sarkola, Taisto;Laposata, Michael
背景资料：最近的实验证据表明，脂肪酸乙酯（FAEE），乙醇的非氧化代谢产物，介导乙醇诱导的器官损伤。先前在大鼠研究中已经显示了胰腺特异性毒性与4-甲基吡唑（4-MP）抑制乙醇氧化代谢后FAEE水平升高之间的直接相关性。我们从32名健康的志愿者中获得了血浆样本，这些志愿者在4-MP或安慰剂摄入，以确定乙醇氧化代谢的体内抑制是否导致乙醇非氧化代谢的转变以及随后增加的FAEE的水平。血浆FAEE分离固相萃取和定量气相色谱-质谱法（GC-MS）。结果：血浆FAEE水平在受试者接受4-MP治疗之前，乙醇消费量升高与血浆FAEE浓度从对照组受试者接受安慰剂之前，乙醇摄入量。4-MP治疗组的FAEE水平增加发生在血乙醇峰值之后，并达到FAEE峰值水平。血液乙醇和血浆FAEE水平之间存在相关性，并且在存在或不存在4-MP的情况下这种相关性持续存在。峰值FAEE值在男性比在女性中更大，有或没有4-MP treatment.Conclusions：我们的研究结果表明，在体内抑制乙醇的氧化代谢使用4-MP的结果在循环中的FAEE浓度增加，产品的非氧化代谢的乙醇。
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.