Nonylphenol Toxicity Evaluation and Discovery of Biomarkers in Rat Urine by a Metabolomics Strategy through HPLC-QTOF-MS

文献类型： 外文期刊

第一作者： Zhang, Yan-Xin

作者： Zhang, Yan-Xin;Yang, Xin;Zou, Pan;Du, Peng-Fei;Wang, Jing;Jin, Fen;Jin, Mao-Jun;She, Yong-Xin;Du, Peng-Fei;Wang, Jing;Jin, Fen;Jin, Mao-Jun;She, Yong-Xin

作者机构：

关键词： nonylphenol;metabolomics;exposure;HPLC-QTOF-MS;biomarker

期刊名称：INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH （ 影响因子：3.39； 五年影响因子：3.789 ）

ISSN： 1660-4601

年卷期： 2016 年 13 卷 5 期

页码：

收录情况： SCI

摘要： Nonylphenol (NP) was quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) in the urine and plasma of rats treated with 0, 50, and 250 mg/kg/day of NP for four consecutive days. A urinary metabolomic strategy was originally implemented by high performance liquid chromatography time of flight mass spectrometry (HPLC-QTOF-MS) to explore the toxicological effects of NP and determine the overall alterations in the metabolite profiles so as to find potential biomarkers. It is essential to point out that from the observation, the metabolic data were clearly clustered and separated for the three groups. To further identify differentiated metabolites, multivariate analysis, including principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA), high-resolution MS/MS analysis, as well as searches of Metlin and Massbank databases, were conducted on a series of metabolites between the control and dose groups. Finally, five metabolites, including glycine, glycerophosphocholine, 5-hydroxytryptamine, malonaldehyde (showing an upward trend), and tryptophan (showing a downward trend), were identified as the potential urinary biomarkers of NP-induced toxicity. In order to validate the reliability of these potential biomarkers, an independent validation was performed by using the multiple reaction monitoring (MRM)-based targeted approach. The oxidative stress reflected by urinary 8-oxo-deoxyguanosine (8-oxodG) levels was elevated in individuals highly exposed to NP, supporting the hypothesis that mitochondrial dysfunction was a result of xenoestrogen accumulation. This study reveals a promising approach to find biomarkers to assist researchers in monitoring NP.

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