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Urinary metabolomic profiling in rats exposed to dietary di(2-ethylhexyl) phthalate (DEHP) using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS)

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Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental chemical with widespread nonoccupational human exposure through multiple ways. Although considerable efforts have been invested to investigate mechanisms of DEHP toxicity, the key metabolic biomarkers of DEHP toxicity remain to be identified. The aim of this study was to assess the urinary metabonomics of dietary DEHP in rats using the technique of ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). Fourteen female Wistar rats were divided into two groups and given increasing dietary doses of DEHP for 30 consecutive days. The urinary metabolite profile was studied using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) enabled clusters to be clearly separated. Eleven principal urinary metabolites were identified as contributing to the clusters. The clusters in the positive electrospray ionization (ESI) mode were xanthurenic acid, kynurenic acid, nonate, N6-methyladenosine, and L-isoleucyl-L-proline. The clusters in the negative ESI mode were hippuric acid, tetrahydrocortisol, citric acid, phenylpropionylglycine, cPA(18:2(9Z, 12Z)/0:0), and LysoPC(14:1(9Z)). The urinary metabonomic changes indicated that exposure to dietary DEHP can affect energy-related metabolism, liver and renal function, fatty acid metabolism, and cause DNA damage in rats. The findings of this study on the urinary metabolites and metabolic pathways of DEHP may form the basis for future studies on the mechanisms of toxicity of this commonly found environmental chemical.

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This work was supported by the National Natural Science Foundation of China (Grant No. 81273079). The present study was conducted in the laboratory of the Key Laboratory of Nutrition and Food Hygiene (Harbin Medical University), Heilongjiang Higher Education Institutions.

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Correspondence to Xiaolin Na or Cheng Wang.

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All animal care and experimental procedures were approved by the Committee on the Ethics of Animal Experiments of the University of Harbin Medical and were in accordance with the policies on the care and use of animals of the current Chinese legislation.

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The authors declare that they have no conflict of interest.

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Responsible editor: Philippe Garrigues

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Dong, X., Zhang, Y., Dong, J. et al. Urinary metabolomic profiling in rats exposed to dietary di(2-ethylhexyl) phthalate (DEHP) using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). Environ Sci Pollut Res 24, 16659–16672 (2017). https://doi.org/10.1007/s11356-017-9091-5

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  • Di(2-ethylhexyl) phthalate
  • Environmental chemical
  • Toxic effects
  • Metabonomics
  • Biomarker
  • Mechanism