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




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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 and 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

Abstract 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





Autor: Yan-Xin Zhang 1, Xin Yang 1,* , Pan Zou 1, Peng-Fei Du 2,3, Jing Wang 2,3,* , Fen Jin 2,3, Mao-Jun Jin 2,3 and Yong-Xin She 2,3

Fuente: http://mdpi.com/



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