Fatty acid ethyl esters (FAEEs), nonoxidative metabolites of ethanol, have been implicated in ethanol-induced heart injury. To assess the in vivo production of FAEEs by myocardial tissue, we used a modified ethanol ablation procedure in pigs. A controlled 60-minute ethanol infusion was administered into the distal left anterior descending coronary artery in seven swine; serial blood sampling of the coronary sinus and peripheral vein before, during, and after infusion allowed measurement of FAEE production and ethanol levels in the coronary sinus and the peripheral circulation. In a single animal, FAEEs were also quantified from nine different sites within the myocardium. FAEEs were produced by the heart within 5 minutes of exposure to ethanol, with very high concentrations of FAEEs detected in coronary sinus blood. Significant variability in amounts of FAEEs was detected in different regions of the heart tissue. A strong correlation was found between coronary sinus FAEEs and ethanol concentration (r = 0.9241, P < 0.00001). FAEE production by the heart after delivery of ethanol into the left anterior descending coronary artery was rapid, reaching levels in the coronary sinus blood 4 to 10 times greater than that found in peripheral blood after ethanol intake. These data demonstrate that FAEEs may be mediators of ethanol-induced cardiotoxicity.

FA ethyl esters (FAEE) are nonoxidative metabolites of ethanol produced by the esterification of FA and ethanol. FAFF have been implicated as mediators of ethanol-induced organ damage in vivo and in vitro , and are markers of ethanol intake. Upon ethanol intake, FAEE are synthesized in the liver and pancreas in significant quantities. There is limited information on the stimulation of FAEE synthesis upon addition of exogenous FA in vitro . HepG2 cells were incubated with ethanol alone, ethanol with 25 μM linoleate, and ethanol with 25 μM stearate. The amount of FAFF in human hepatoblastoma (HepG2) cells was determined 1–3 h after ethanol and FA addition. Stearate increased the FAEE concentration in HepG2 cells when incubated with the cells for 1 h, whereas linoleate did not increase the cellular FAEE concentration at any time. Ethyl palmitate, ethyl stearate, and ethyl oleate were the predominant FAEE species identified in all cases, independent of the specific supplemental FA added to the medium.

Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, have been shown to be mediators of ethanol-induced cell injury and their presence in the blood and tissues is a marker of ethanol intake. Recently, it has been shown that FAEE are produced within seconds of infusion of ethanol into the heart, when using a protocol similar to that used for myocardial ablation. This raises the possibility that the mechanism for the death of myocytes in cardiac ablation involves the generation of toxic FAEE. It has also been recently demonstrated that chronic alcoholics have a high concentration of a specific FAEE species--ethyl oleate. The use of the serum ethyl oleate concentration may be helpful in differentiating binge drinkers from chronic alcoholics.

BACKGROUND:Fatty acid ethyl esters (FAEEs) are nonoxidative metabolites of ethanol produced by the esterification of fatty acids and ethanol. FAEEs have been implicated as mediators of ethanol-induced organ damage in vivo and in vitro. They are detectable in the blood and in many organs after ethanol ingestion, and on this basis they are useful markers of ethanol intake in living patients as well as subjects at autopsy. FAEEs found in human plasma after ethanol ingestion bind to lipoproteins and albumin.METHODS:In this study, we used a hepatoblastoma cell model (HepG2) to determine if lipoproteins or albumin stimulates the synthesis and/or secretion of FAEEs from HepG2 cells. Because FAEEs have been shown to decrease HepG2 cellular proliferation and protein synthesis, their removal from cells potentially could reestablish normal cell activity. HepG2 cells were incubated with 100 mM ethanol and 6 nM 3H oleic acid to generate 3H-FAEEs within the cells. Dose response and time course studies were performed by using low density lipoproteins, high density lipoproteins, and albumin as FAEE acceptors.RESULTS:The results indicate that FAEEs are extracted efficiently by each of these FAEE carriers and that FAEE synthesis also is stimulated by the addition of FAEE carriers to the extracellular medium.CONCLUSION:These observations indicate that lipoproteins and albumin can extract ethyl esters from HepG2 cells and thereby may limit alcohol-induced liver damage.

Fatty acid ethyl esters (FAEEs) are cytotoxic nonoxidative metabolites of ethanol that are produced by esterification of alcohol and fatty acids (1)(2)(3). After ethanol intake, FAEEs are found mainly in the liver, pancreas, heart, and brain, which are the major organs adversely affected by ethanol intake (4)(5). FAEEs are detectable in the blood for up to 24 h after consumption of ethanol to at least 600 mg/L (6)(7)(8), making the presence of FAEEs in blood a useful marker for ethanol intake. This investigation presents the results of studies on the effects of collection tube, storage time, and storage temperature on FAEE concentrations in blood, with the goal of creating a reliable clinical assay for serum and plasma FAEE quantification. Four volunteers participated in this study. Each subject was given a weight-adjusted amount of 100-proof vodka mixed with fruit juice in a 1:3 ratio (8). The vodka-juice beverage was divided into nine equal aliquots, which were administered every 10 min over a 90-min time period. After the last aliquot was drunk, blood samples were collected in four different 5-mL Vacutainer Tubes from each subject to assess the influence of the collection tube …

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