Identifying Early Urinary Metabolic Changes with Long-Term Environmental Exposure to Cadmium by Mass-Spectrometry-Based Metabolomics
Identifying Early Urinary Metabolic Changes with Long-Term Environmental Exposure to Cadmium by Mass-Spectrometry-Based Metabolomics
复制标题
通过基于质谱的代谢组学识别长期环境暴露于镉的早期尿液代谢变化
DOI：
10.1021/es500750w
复制
发表时间：
2014-06-03
影响因子：
11.4
通讯作者：
Ong, Choon Nam
中科院分区：
文献类型：
--
作者：
Gao, Yanhong;Lu, Yonghai;Ong, Choon Nam
镉（Cd）是一种常见的环境污染物，尿镉（UCd）通常被用作暴露的标志；然而，我们对Cd暴露引起的相关尿代谢变化的认识尚不清楚。在这项研究中，我们应用基于质谱的代谢组学方法来评估长期环境Cd暴露的人的尿液代谢变化，旨在确定早期生物标志物来评估Cd肾毒性。本文采用液相色谱四极杆飞行时间质谱（LC-Q-ToF-MS）和气相色谱质谱（GC MS）对94例未吸烟女性尿液进行了分析，年龄在44 ~ 70岁，UCd在0.20 ~ 68.67 μ g/L之间。发现代谢产物与氨基酸代谢（l-谷氨酰胺、l-胱氨酸、l-酪氨酸、n -甲基- l-组氨酸、l-组氨酸二醇、牛磺酸、苯乙酰谷氨酰胺、马粪酸和焦谷氨酸）、半乳糖代谢（d -半乳糖和肌醇）、嘌呤代谢（黄嘌呤、尿素和脱氧腺苷单磷酸）、肌酸途径（肌酸和肌酐）和类固醇激素生物合成(17- α -羟孕酮、四氢可的松、雌酮、在UCd水平高于5 μ g/L的人群中，皮质醇含量显著升高。此外，我们注意到，当UCd浓度为>= 2 μ g/L时，n -甲基-L-组氨酸水平已经开始升高。总的研究结果表明，代谢组学为揭示镉暴露导致的代谢变化提供了一种有用的方法。
Cadmium (Cd) is a common environmental pollutant, and urinary Cd (UCd) is generally used as a marker of exposure; however, our understanding on the related urinary metabolic changes caused by Cd exposure is still not clear. In this study, we applied a mass-spectrometry-based metabolomic approach to assess the urinary metabolic changes in human with long-term environmental Cd exposure, aimed to identify early biomarkers to assess Cd nephrotoxicity. Urine samples from 94 female never smokers aged 44-70 with UCd in the range of 0.20-68.67 mu g/L were analyzed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS) and gas chromatography mass spectrometry (GC MS). It was found that metabolites related to amino acid metabolism (L-glutamine, L-cystine, L-tyrosine, N-methyl-L-histidine, L-histidinol, taurine, phenylacetylglutamine, hippurate, and pyroglutamic acid), galactose metabolism (D-galactose and myo-inositol), purine metabolism (xanthine, urea, and deoxyadenosine monophosphate), creatine pathway (creatine and creatinine), and steroid hormone biosynthesis (17-alpha-hydroxyprogesterone, tetrahydrocortisone, estrone, and corticosterone) were significantly higher among those with a UCd level higher than 5 mu g/L. Moreover, we noticed that the level of N-methyl-L-histidine had already started to elevate among individuals with a UCd concentration of >= 2 mu g/L. The overall findings illustrate that metabolomics offer a useful approach for revealing metabolic changes as a result of Cd exposure.