First Time View on Human Metabolome Changes after a Single Intake of 3,4-Methylenedioxymethamphetamine in Healthy Placebo-Controlled Subjects

被引:13
作者
Boxler, Martina I. [1 ]
Liechti, Matthias E. [2 ]
Schmid, Yasmin [2 ]
Kraemer, Thomas [1 ]
Steuer, Andrea E. [1 ]
机构
[1] Univ Zurich, Zurich Inst Forens Med, Dept Forens Pharmacol & Toxicol, Winterthurerstr 190-52, CH-8057 Zurich, Switzerland
[2] Univ Hosp Basel, Div Clin Pharmacol & Toxicol, Dept Biomed, Psychopharmacol Res,Dept Clin Res, CH-4031 Basel, Switzerland
基金
瑞士国家科学基金会;
关键词
3,4-methylenedioxymethamphetamine (MDMA); ecstasy; targeted metabolomics; biocrates; methionine; placebo-controlled; PLASMA-CONCENTRATIONS; ENDOTHELIAL-CELLS; AMINO-ACIDS; HUMAN SERUM; MDMA; METHIONINE; OXIDATION; ECSTASY; BLOOD; LYSOPHOSPHATIDYLCHOLINE;
D O I
10.1021/acs.jproteome.7b00294
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 IS subjects taken at four different time points were analyzed with the commercially available AbsolutelDQkit (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.
引用
收藏
页码:3310 / 3320
页数:11
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