期刊
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
卷 66, 期 -, 页码 287-297出版社
ELSEVIER
DOI: 10.1016/j.jpba.2012.03.045
关键词
Metabonomics; Exposure; Phthalate; Polychlorinated biphenyl
资金
- Chinese Academy of Sciences (CAS) [KZCX2-EW-QN408, 09i4061a70]
- Xiamen Science and Technology Fund [3502Z20112017]
Humans undergo simultaneous daily exposure to a multitude of endocrine-disrupting compounds (EDCs). In present study, after combined exposure to endocrine disruptors DEHP and Aroclor 1254 for 12 days, a liquid chromatography/time-of-flight mass spectrometer method combining both reversed-phase (RP) and hydrophilic interaction chromatography (HILIC) separations was carried out to investigate the metabolic responses in mice. The metabolic profiles of endogenous metabolites could differentiate the dose and control groups in both RPLC and HILIC modes. Moreover, the male mice and female mice in different groups could be obviously clustered in their own regions with combined model. Fourteen lysoPCs, PC(18:4/18:1), lysoPE(18:2/0:0), phenylalanine and tryptophan were identified as potential biomarkers for the combined toxicity of DEHP and Aroclor 1254. Different change trends could be observed for the identified lysoPCs, due to their different levels of uptake and metabolism in mice. Moreover, gender-specific differences in several lysoPCs (e.g. lysoPC(18:0), lysoPC(22:6), lysoPC(20:3), and PC(18:4/18:1)) were observed for treated mice. The metabonomic results indicated the combined exposure led to a disturbance of lipid metabolism. The mRNA expressions of PLA2, ACOX1, CPT1, FAS and SCD1 involved in lipid metabolism were investigated. Among them, significant increases of FAS and SCD1 expressions in the liver induced by the exposure could be observed for both male and female mice, contributing to the hepatic lipid accumulation in mice. Besides lipid metabolism, tryptophan metabolism and phenylalanine metabolism may also be involved with the toxic responses to these EDCs. The present study not only improves the understanding of the combined toxicity of phthalates and PCBs but also shows that the metabonomic approach may prove to be a promising technique for the toxicity research of EDCs. (C) 2012 Elsevier B.V. All rights reserved.
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