PMID- 27187439 OWN - NLM STAT- MEDLINE DCOM- 20170703 LR - 20191210 IS - 1660-4601 (Electronic) IS - 1661-7827 (Print) IS - 1660-4601 (Linking) VI - 13 IP - 5 DP - 2016 May 14 TI - Nonylphenol Toxicity Evaluation and Discovery of Biomarkers in Rat Urine by a Metabolomics Strategy through HPLC-QTOF-MS. LID - 10.3390/ijerph13050501 [doi] LID - 501 AB - 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. FAU - Zhang, Yan-Xin AU - Zhang YX AD - School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China. yanxinzhangbj@163.com. FAU - Yang, Xin AU - Yang X AD - School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China. yangxin@hit.edu.cn. FAU - Zou, Pan AU - Zou P AD - School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China. zoupan0601@163.com. FAU - Du, Peng-Fei AU - Du PF AD - 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. dupengfei2011@163.com. AD - Key Laboratory of Agro-Product Safety and Quality, Ministry of Agriculture, Beijing 100081, China. dupengfei2011@163.com. FAU - Wang, Jing AU - Wang J AD - 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. w_jing2001@126.com. AD - Key Laboratory of Agro-Product Safety and Quality, Ministry of Agriculture, Beijing 100081, China. w_jing2001@126.com. FAU - Jin, Fen AU - Jin F AD - 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. jinfenbj@163.com. AD - Key Laboratory of Agro-Product Safety and Quality, Ministry of Agriculture, Beijing 100081, China. jinfenbj@163.com. FAU - Jin, Mao-Jun AU - Jin MJ AD - 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. katonking@163.com. AD - Key Laboratory of Agro-Product Safety and Quality, Ministry of Agriculture, Beijing 100081, China. katonking@163.com. FAU - She, Yong-Xin AU - She YX AD - 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. 0891syx@163.com. AD - Key Laboratory of Agro-Product Safety and Quality, Ministry of Agriculture, Beijing 100081, China. 0891syx@163.com. LA - eng PT - Journal Article DEP - 20160514 PL - Switzerland TA - Int J Environ Res Public Health JT - International journal of environmental research and public health JID - 101238455 RN - 0 (Biomarkers) RN - 0 (Phenols) RN - 333DO1RDJY (Serotonin) RN - 4Y8F71G49Q (Malondialdehyde) RN - 60M22SGW66 (Glycerylphosphorylcholine) RN - 79F6A2ILP5 (nonylphenol) RN - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine) RN - 8DUH1N11BX (Tryptophan) RN - G9481N71RO (Deoxyguanosine) RN - TE7660XO1C (Glycine) SB - IM MH - 8-Hydroxy-2'-Deoxyguanosine MH - Animals MH - Biomarkers/blood/urine MH - Chromatography, High Pressure Liquid/methods MH - Deoxyguanosine/analogs & derivatives/urine MH - Discriminant Analysis MH - Female MH - Glycerylphosphorylcholine/urine MH - Glycine/urine MH - Least-Squares Analysis MH - Malondialdehyde/urine MH - Mass Spectrometry/methods MH - Metabolomics MH - Multivariate Analysis MH - Oxidative Stress/drug effects MH - Phenols/*toxicity MH - Principal Component Analysis MH - Rats, Sprague-Dawley MH - Reproducibility of Results MH - Serotonin/urine MH - Tryptophan/urine PMC - PMC4881126 OTO - NOTNLM OT - HPLC-QTOF-MS OT - biomarker OT - exposure OT - metabolomics OT - nonylphenol EDAT- 2016/05/18 06:00 MHDA- 2017/07/04 06:00 PMCR- 2016/05/01 CRDT- 2016/05/18 06:00 PHST- 2016/03/22 00:00 [received] PHST- 2016/05/08 00:00 [revised] PHST- 2016/05/10 00:00 [accepted] PHST- 2016/05/18 06:00 [entrez] PHST- 2016/05/18 06:00 [pubmed] PHST- 2017/07/04 06:00 [medline] PHST- 2016/05/01 00:00 [pmc-release] AID - ijerph13050501 [pii] AID - ijerph-13-00501 [pii] AID - 10.3390/ijerph13050501 [doi] PST - epublish SO - Int J Environ Res Public Health. 2016 May 14;13(5):501. doi: 10.3390/ijerph13050501.