Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, USA.
Alcohol Clin Exp Res. 2021 Apr;45(4):689-696. doi: 10.1111/acer.14584. Epub 2021 Apr 19.
Phosphatidylethanol (PEth) homologs are ethanol metabolites used to identify and monitor alcohol drinking in humans. In this study, we measured levels of the 2 most abundant homologs, PEth 16:0/18:1 and PEth 16:0/18:2, in whole blood samples from rhesus macaque monkeys that drank ethanol daily ad libitum to assess the relationship between PEth levels and recent ethanol exposure in this animal model.
Blood samples were obtained from The Monkey Alcohol Tissue Research Resource. The monkeys were first induced to consume 4% (w/v) ethanol in water from a panel attached to their home cage. Then, monkeys were allowed to drink ethanol and water ad libitum 22 h daily for 12 months and the daily amount of ethanol each monkey consumed was measured. Whole, uncoagulated blood was collected from each animal at the end of the entire experimental procedure. PEth 16:0/18:1 and PEth 16:0/18:2 levels were analyzed by HPLC with tandem mass spectrometry, and the ethanol consumed during the preceding 14 days was measured. Combined PEth was the sum of the concentrations of both homologs.
Our results show that (1) PEth accumulates in the blood of rhesus monkeys after ethanol consumption; (2) PEth homolog levels were correlated with the daily average ethanol intake during the 14-day period immediately preceding blood collection; (3) the application of established human PEth 16:0/18:1 cutoff concentrations indicative of light social or no ethanol consumption (<20 ng/ml), moderate ethanol consumption (≥ 20 and < 200 ng/ml) and heavy ethanol consumption (≥ 200 ng/ml) predicted significantly different ethanol intake in these animals. PEth homologs were not detected in ethanol-naïve controls.
This study confirms that PEth is a sensitive biomarker for ethanol consumption in rhesus macaque monkeys. This nonhuman primate model may prove useful in evaluating sources of variability previously shown to exist between ethanol consumption and PEth homolog levels among humans.
磷脂酰乙醇(PEth)同系物是用于鉴定和监测人体饮酒的乙醇代谢物。在这项研究中,我们测量了自由饮用乙醇的恒河猴全血样本中两种最丰富的同系物,PEth 16:0/18:1 和 PEth 16:0/18:2 的水平,以评估该动物模型中 PEth 水平与近期乙醇暴露之间的关系。
从猴酒精组织研究资源获得血液样本。首先将猴子诱导饮用附着在其笼舍上的面板中的 4%(w/v)乙醇水。然后,让猴子每天自由饮用乙醇和水 22 小时,持续 12 个月,并测量每只猴子每天消耗的乙醇量。在整个实验过程结束时,从每个动物采集未凝固的全血。通过 HPLC 与串联质谱法分析 PEth 16:0/18:1 和 PEth 16:0/18:2 水平,测量在过去 14 天内消耗的乙醇量。合并的 PEth 是两种同系物浓度的总和。
我们的结果表明:(1)PEth 在恒河猴饮酒后在血液中积累;(2)PEth 同系物水平与采血前 14 天内的日平均乙醇摄入量相关;(3)应用人类 PEth 16:0/18:1 截断浓度来指示轻度社交或无乙醇摄入(<20ng/ml)、中度乙醇摄入(≥20 且 <200ng/ml)和重度乙醇摄入(≥200ng/ml),可预测这些动物中显著不同的乙醇摄入量。在未接触乙醇的对照中未检测到 PEth 同系物。
这项研究证实 PEth 是恒河猴乙醇消耗的敏感生物标志物。这种非人类灵长类动物模型可能有助于评估先前在人类中存在的乙醇消耗和 PEth 同系物水平之间的变异性来源。