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死后代谢组学揭示酰基肉碱作为致命性羟考酮相关中毒的潜在生物标志物。

Postmortem Metabolomics Reveal Acylcarnitines as Potential Biomarkers for Fatal Oxycodone-Related Intoxication.

作者信息

Elmsjö Albert, Söderberg Carl, Jakobsson Gerd, Green Henrik, Kronstrand Robert

机构信息

Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 587 58 Linköping, Sweden.

Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Linköping University, 581 83 Linköping, Sweden.

出版信息

Metabolites. 2022 Jan 25;12(2):109. doi: 10.3390/metabo12020109.

Abstract

Postmortem metabolomics has recently been suggested as a potential tool for discovering new biological markers able to assist in death investigations. Interpretation of oxycodone concentrations in postmortem cases is complicated, as oxycodone tolerance leads to overlapping concentrations for oxycodone intoxications versus non-intoxications. The primary aim of this study was to use postmortem metabolomics to identify potential endogenous biomarkers that discriminate between oxycodone-related intoxications and non-intoxications. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry data from 934 postmortem femoral blood samples, including oxycodone intoxications and controls positive and negative for oxycodone, were used in this study. Data were processed and evaluated with XCMS and SIMCA. A clear trend in group separation was observed between intoxications and controls, with a model sensitivity and specificity of 80% and 76%. Approximately halved levels of short-, medium-, and long-chain acylcarnitines were observed for oxycodone intoxications in comparison with controls ( < 0.001). These biochemical changes seem to relate to the toxicological effects of oxycodone and potentially acylcarnitines constituting a biologically relevant biomarker for opioid poisonings. More studies are needed in order to elucidate the potential of acylcarnitines as biomarker for oxycodone toxicity and their relation to CNS-depressant effects.

摘要

最近,尸检代谢组学被认为是一种潜在工具,可用于发现有助于死亡调查的新生物标志物。在尸检案例中,羟考酮浓度的解读很复杂,因为羟考酮耐受性会导致羟考酮中毒与未中毒的浓度出现重叠。本研究的主要目的是利用尸检代谢组学来识别区分羟考酮相关中毒与未中毒的潜在内源性生物标志物。本研究使用了来自934份尸检股血样本的超高效液相色谱-四极杆飞行时间质谱数据,这些样本包括羟考酮中毒案例以及羟考酮阳性和阴性对照。数据采用XCMS和SIMCA进行处理和评估。在中毒案例与对照之间观察到了明显的分组分离趋势,模型的敏感性和特异性分别为80%和76%。与对照相比,羟考酮中毒案例中短链、中链和长链酰基肉碱的水平大约减半(<0.001)。这些生化变化似乎与羟考酮的毒理学效应有关,并且酰基肉碱可能构成阿片类药物中毒的生物学相关生物标志物。为了阐明酰基肉碱作为羟考酮毒性生物标志物的潜力及其与中枢神经系统抑制作用的关系,还需要更多研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d043/8878426/85b437445269/metabolites-12-00109-g001.jpg

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