Nonylphenol Toxicity Evaluation and Discovery of Biomarkers in Rat Urine by a Metabolomics Strategy through HPLC-QTOF-MS
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Treatment
2.2. Monitoring the NP Exposure Levels
2.2.1. Sample Preparation
2.2.2. NP Analysis by HPLC-MS/MS
2.3. Metabolomics Analysis in Urine with HPLC-QTOF-MS
2.3.1. Sample Preparation
2.3.2. HPLC-QTOF-MS Data Acquisition
2.4. Processing and Statistical Analysis of MS Spectra Data
2.4.1. Data Extraction and Normalization
2.4.2. Multivariate Data Analysis
2.5. Identification of Metabolites
2.6. HPLC-MS/MS-Based Validation Test
2.7. Quantitation of the Oxidative Stress Biomarker 8-oxo-deoxyguanosine (8-oxodG) in Urine
3. Results
3.1. Determination of the Level of Exposure to Pesticides
3.2. Acquisition of Mass Spectrum Data
3.3. Dose Selection
3.4. Multivariate Data Analysis of HPLC-TOF-MS Spectra
3.5. Biomarkers Identification
3.6. Potential Biomarkers Validation by Targeted Metabolomics Based on HPLC-MS/MS
3.7. Association of NP Exposure and Oxidative Stress
4. Discussion
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
NP | Nonylphenol |
ESI | Electrospray ionization |
MS | Mass spectrometry |
Q-TOF MS | Quadrupole time-of-flight mass spectrometer |
HPLC | Ultra high performance liquid chromatography |
IDA | information-dependent acquisition |
MVDA | multivariate data analysis |
PCA | principal component analysis |
OPLS-DA | orthogonal partial least-squares discrimination analysis |
8-oxodG | 8-oxo-deoxyguanosine |
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Metabolite | Molecular Formula | VIP Score | p-Value | Monitored Structure | Monitored M.W. | Exact Mass | Trend |
---|---|---|---|---|---|---|---|
5-hydroxytryptamine | C10H12N2O | 2.59281 | 0.036 | M + H | 177.0869 | 176.0950 | upward |
tryptophan | C11H12N2O2 | 2.39113 | 0.027 | M + H | 205.0918 | 204.0899 | downward |
glycine | C2H5NO2 | 2.40796 | 0.041 | M + H | 76.0335 | 75.0320 | upward |
glycerophosphocholine | C8H20NO6P | 2.2673 | 0.032 | M + H | 258.1031 | 257.1028 | upward |
malonaldehyde | C3H4O2 | 2.89664 | 0.023 | M + H | 73.0634 | 72.0211 | upward |
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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
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 StyleZhang, 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