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长期低浓度职业接触丙烯酰胺人群尿液代谢组学研究。

A urinary metabolomic study from subjects after long-term occupational exposure to low concentration acrylamide using UPLC-QTOF/MS.

机构信息

Department of Occupational Health, Public Health College, Harbin Medical University, Harbin, PR China.

College of Medical Technology, Shanghai University of Medicine & Health Sciences, Shanghai, PR China.

出版信息

Arch Biochem Biophys. 2020 Mar 15;681:108279. doi: 10.1016/j.abb.2020.108279. Epub 2020 Jan 23.

Abstract

Because long-term occupational exposure to low concentrations of acrylamide (ACR) has the potential to cause neurological damage, it is important to identify biomarkers that can be used to evaluate this risk. In the present study, urine metabolomics of the ACR-exposed and non-exposed groups to identify potential metabolites was carried out using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry. Serum biochemical indexes of the exposed and non-exposed groups were also determined. Principal component analysis showed a differential separation between exposed group and non-exposed group and a total of 7 metabolites were identified in positive and negative ionization modes; Area under curve of anthranilic acid, β-guanidinopropionic acid and mesobilirubinogen were 0.980, 0.843 and 0.801 respectively and these metabolites showed high sensitivity and specificity. The 13 biochemical indexes were divided into three classes based on physiological functions. Only biomarkers of dysregulated liver function including alanine aminotransferase, aspartic transaminase, total bilirubin, direct bilirubin and triglyceride were significantly higher in the exposed group than in the non-exposed group. This study identifies important related metabolic changes in the bodies of workers after long-term occupational exposure to low concentration ACR and suggests new biomarkers of nervous system injury caused by ACR. The study also provides a sound basis for exploring the biochemical mechanisms and metabolic pathways of nervous system toxicity caused by ACR.

摘要

由于长期职业性接触低浓度丙烯酰胺(ACR)有潜在的神经损伤风险,因此识别可用于评估该风险的生物标志物非常重要。本研究采用超高效液相色谱-四极杆飞行时间质谱联用技术对 ACR 暴露组和非暴露组的尿液代谢组进行了分析,以鉴定潜在的代谢物。还测定了暴露组和非暴露组的血清生化指标。主成分分析显示,暴露组和非暴露组之间存在差异分离,在正、负离子模式下共鉴定出 7 种代谢物;邻氨基苯甲酸、β-胍基丙酸和粪卟啉原Ⅲ的曲线下面积分别为 0.980、0.843 和 0.801,这些代谢物具有较高的灵敏度和特异性。根据生理功能将 13 项生化指标分为三类。仅暴露组中与肝功能失调相关的生物标志物如丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、总胆红素、直接胆红素和甘油三酯显著高于非暴露组。本研究确定了长期职业性接触低浓度 ACR 后工人体内重要的相关代谢变化,并提示了 ACR 引起的神经系统损伤的新生物标志物。该研究还为探索 ACR 引起的神经系统毒性的生化机制和代谢途径提供了坚实的基础。

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