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采用气相色谱-质谱联用技术分析急性百草枯中毒患者血浆代谢组学特征。

Metabolomics profile of plasma in acute diquat-poisoned patients using gas chromatography-mass spectrometry.

机构信息

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

出版信息

Food Chem Toxicol. 2023 Jun;176:113765. doi: 10.1016/j.fct.2023.113765. Epub 2023 Apr 5.

Abstract

Diquat (DQ) has been confirmed to be toxic to humans and responsible for severe health impairment. While to date, very little is known about the toxicological mechanisms of DQ. Thus, investigations to discover the toxic targets and potential biomarkers of DQ poisoning are urgently needed. In this study, a metabolic profiling analysis was conducted to reveal the changes of metabolites of plasma and find out the potential biomarkers of DQ intoxication by GC-MS. First, multivariate statistical analysis demonstrated that acute DQ poisoning can lead to metabolomic changes in human plasma. Then, metabolomics studies showed that 31 of the identified metabolites were significantly altered by DQ. Pathway analysis indicated that three primarily metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, and phenylalanine metabolism were affected by DQ, resulting in the perturbations of phenylalanine, tyrosine, taurine, and cysteine. Finally, the results of receiver operating characteristic analysis showed the above four metabolites could be used as reliable tools for the diagnosis and severity assessments of DQ intoxication. These data provided the theoretical basis for basic research to understand the potential mechanisms of DQ poisoning, and also identified the desirable biomarkers with great potential for clinical applications.

摘要

敌草快(DQ)已被证实对人体有毒,可导致严重的健康损害。尽管迄今为止,人们对 DQ 的毒理学机制知之甚少。因此,迫切需要开展研究以发现 DQ 中毒的毒性靶标和潜在生物标志物。在这项研究中,我们采用 GC-MS 进行代谢组学分析,以揭示血浆代谢物的变化情况,并找到 DQ 中毒的潜在生物标志物。首先,多变量统计分析表明,急性 DQ 中毒可导致人血浆代谢组学发生变化。然后,代谢组学研究表明,31 种鉴定出的代谢物受 DQ 显著影响。途径分析表明,三个主要代谢途径(苯丙氨酸、酪氨酸和色氨酸生物合成、牛磺酸和次牛磺酸代谢以及苯丙氨酸代谢)受到 DQ 的影响,导致苯丙氨酸、酪氨酸、牛磺酸和半胱氨酸发生紊乱。最后,接受者操作特征分析的结果表明,上述四种代谢物可作为诊断和严重程度评估 DQ 中毒的可靠工具。这些数据为深入了解 DQ 中毒的潜在机制提供了理论基础,也为临床应用确定了有很大潜力的理想生物标志物。

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