Ethyl arachidonate is the predominant fatty acid ethyl ester in the brains of alcohol‐intoxicated subjects at autopsy

Abstract

The role of fatty acid ethyl esters (FAEE), the nonoxidative ethanol metabolites, as mediators of alcohol-induced organ damage is increasingly being recognized. FAEE are detectable in the blood and in liver and adipose tissue after ethanol ingestion, and on that basis, FAEE can be used as markers of ethanol intake. In this study, 10 samples of human brain were collected at autopsy at the Massachusetts Medical Examiner's Office and analyzed for FAEE. FAEE were isolated and quantified as mass per gram of wet weight. The blood ethanol level was also obtained in each case along with the other drugs detected in routine postmortem toxicology screening tests. Ethyl arachidonate was the predominant FAEE species in the brain, representing up to 77.4% of total FAEE in the brain. The percent age of ethyl arachidonate of the total FAEE in the brain was significantly higher than what has been found in all other organs and tissues previously analyzed. Linoleate, the precursor of arachidonate, was a poor substrate for FAEE synthesis, as the percentage of ethyl linoleate of the total FAEE content was extremely low. Thus, this reflects preferred incorporation of arachidonate into newly synthesized FAEE in the brain. Since arachidonate is derived from linoleate, which is depleted in FAEE while arachidonate is enriched, the synthesis of FAEE may be linked to the desaturation and elongation of linoleate to arachidonate.

Human alcohol-related neuropathology

“…Despite decades of awareness of the neurological and neuropathological effects of heavy alcohol abuse, we are still lagging in our understanding of disease spectra and mechanisms, in part due to inadequate clinical data, and overlap between alcohol-related and other metabolic diseases. However, with growing availability of long-lasting biochemical markers of alcohol exposure such as fatty acid ethyl ester [123] and phosphatidylethanol [67], future studies will be better equipped to characterize ethanol’s effects in both developing and mature nervous systems.…”

investigation into fatty acid ethyl esters in mouse brains after ethanol treatment: detection, quantification, and potential toxicity

“…In all dose groups, in both the rest of the brain and cerebellum, AAEE was the predominant FAEE, accounting for between 43-70% of the total FAEE Cmax, Figure 58, in the brain, and between 52% and 67% of the AUClast. These percentages are similar to the percentages of AAEE measured by Refaai et al, 2003, in the human brain, where AAEE accounted for up to 77.4% of the total FAEE. In studies by Laposata et al, 1987, the capacities of different areas of the human brain were evaluated for their ability to synthesize FAEE.…”

“…As an initial goal, the intent was to determine if AAEE or other FAEEs could be detected in whole brain from mice dosed acutely with ethanol. While there are reports that AAEE has been detected in humans intoxicated at the time of death (Refaai, 2003), there are no reports of AAEE being detected in mice brains after ethanol treatment.…”

“…Arachidonic acid (AA) -AAEEknown to be generated in the brain (Refaai et al, 2003) SAEE-known to be present in the liver (Laposata, 2000).…”