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

by 1, 1,*, 1, 2,3, 2,3,*, 2,3, 2,3 and 2,3
1
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China
2
Key Laboratory of Agro-Product Quality and Safety, Institute of Quality Standard & Testing Technology for Agro-Product, Chinese Academy of Agricultural Sciences, Beijing 100081, China
3
Key Laboratory of Agro-Product Safety and Quality, Ministry of Agriculture, Beijing 100081, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Huang-Tsung Chang
Int. J. Environ. Res. Public Health 2016, 13(5), 501; https://doi.org/10.3390/ijerph13050501
Received: 22 March 2016 / Revised: 8 May 2016 / Accepted: 10 May 2016 / Published: 14 May 2016
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. View Full-Text
Keywords: nonylphenol; metabolomics; exposure; HPLC-QTOF-MS; biomarker nonylphenol; metabolomics; exposure; HPLC-QTOF-MS; biomarker
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MDPI and ACS Style

Zhang, Y.-X.; Yang, X.; Zou, P.; Du, P.-F.; Wang, J.; Jin, F.; Jin, M.-J.; She, Y.-X. Nonylphenol Toxicity Evaluation and Discovery of Biomarkers in Rat Urine by a Metabolomics Strategy through HPLC-QTOF-MS. Int. J. Environ. Res. Public Health 2016, 13, 501. https://doi.org/10.3390/ijerph13050501

AMA Style

Zhang Y-X, Yang X, Zou P, Du P-F, Wang J, Jin F, Jin M-J, She Y-X. Nonylphenol Toxicity Evaluation and Discovery of Biomarkers in Rat Urine by a Metabolomics Strategy through HPLC-QTOF-MS. International Journal of Environmental Research and Public Health. 2016; 13(5):501. https://doi.org/10.3390/ijerph13050501

Chicago/Turabian Style

Zhang, Yan-Xin, Xin Yang, Pan Zou, Peng-Fei Du, Jing Wang, Fen Jin, Mao-Jun Jin, and Yong-Xin She. 2016. "Nonylphenol Toxicity Evaluation and Discovery of Biomarkers in Rat Urine by a Metabolomics Strategy through HPLC-QTOF-MS" International Journal of Environmental Research and Public Health 13, no. 5: 501. https://doi.org/10.3390/ijerph13050501

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