Department of Forensic Pharmacology & Toxicology, Zurich Institute of Forensic Medicine, University of Zurich ,Winterthurerstrasse 190/52, 8057 Zurich, Switzerland.
Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, Department of Clinical Research, University Hospital Basel , 4031 Basel, Switzerland.
J Proteome Res. 2017 Sep 1;16(9):3310-3320. doi: 10.1021/acs.jproteome.7b00294. Epub 2017 Aug 9.
3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is widely consumed recreationally. Little is known about its effects on the human metabolome. Mapping biochemical changes after drug exposure can complement traditional approaches by revealing potential biomarkers of organ toxicity or discovering new metabolomic features in a time- and dose-dependent manner. We aimed to analyze for the first time plasma samples from a randomized, double-blind, placebo-controlled crossover study in healthy adults to explore changes in endogenous plasma metabolites following a single intake of MDMA. Plasma samples from 15 subjects taken at four different time points were analyzed with the commercially available AbsoluteIDQ kit (Biocrates). Time series analysis revealed a total of nine metabolites, which showed a significant concentration change after MDMA administration compared with placebo. Paired t tests of the single time points showed statistically significant concentration changes mainly of glycerophospholipids and the metabolic ratio of methionine-sulfoxide over methionine. Changes of this metabolic ratio may be indicative for changes in systemic oxidative stress levels, and the increased amount of glycerophospholipids could be interpreted as an upregulation of energy production. Baseline samples within the experimental study design were crucial for evaluation of metabolomics data as interday individuality within subjects was high otherwise resulting in overestimations of the findings.
3,4-亚甲二氧基甲基苯丙胺（MDMA；“摇头丸”）被广泛滥用。目前对于其对人体代谢组的影响知之甚少。药物暴露后对生化变化进行映射可以通过揭示潜在的器官毒性生物标志物或发现新的代谢组学特征来补充传统方法，从而以时间和剂量依赖的方式进行。我们旨在首次分析来自健康成年人的一项随机、双盲、安慰剂对照交叉研究的血浆样本，以探索单次 MDMA 摄入后内源性血浆代谢物的变化。使用市售的 AbsoluteIDQ 试剂盒（Biocrates）分析了来自 15 名受试者的四个不同时间点的血浆样本。时间序列分析共显示了 9 种代谢物，与安慰剂相比，这些代谢物在 MDMA 给药后浓度发生了显著变化。对单个时间点的配对 t 检验显示，主要是甘油磷脂和蛋氨酸亚砜与蛋氨酸的代谢比发生了统计学上显著的浓度变化。这种代谢比的变化可能表明全身氧化应激水平的变化，甘油磷脂的增加量可解释为能量产生的上调。否则，实验研究设计中的基线样本对于代谢组学数据的评估至关重要，因为受试者之间的日间个体差异很高，会导致对结果的高估。
