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Open AccessArticle

Metabolomics Reveals Metabolic Changes Caused by Low-Dose 4-Tert-Octylphenol in Mice Liver

by Kun Zhou 1,2,†, Xingwang Ding 1,2,†, Jing Yang 3,†, Yanhui Hu 4, Yun Song 1,2, Minjian Chen 1,2,*, Rongli Sun 5, Tianyu Dong 1,2, Bo Xu 1,2, Xiumei Han 1,2, Keqin Wu 1,2, Xiaoling Zhang 6, Xinru Wang 1,2 and Yankai Xia 1,2,*
1
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China
2
Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
3
Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
4
Safety Assessment and Research Center for Drug, Pesticide, and Veterinary Drug of Jiangsu Province, School of Public Health, Nanjing Medical University, Nanjing 211166, China
5
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
6
Department of Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Environ. Res. Public Health 2018, 15(12), 2686; https://doi.org/10.3390/ijerph15122686
Received: 12 October 2018 / Revised: 19 November 2018 / Accepted: 25 November 2018 / Published: 28 November 2018
(This article belongs to the Section Environmental Health)
Background: Humans are constantly exposed to low concentrations of 4-tert-octylphenol (OP). However, studies investigating the effects of low-dose OP on the liver are scarce, and the mechanism of these effects has not been thoroughly elucidated to date. Methods: Adult male institute of cancer research (ICR) mice were exposed to low-dose OP (0, 0.01 and 1 μg/kg/day) for 7 consecutive days. Weights of mice were recorded daily during the experiment. Blood serum levels of OP, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined, and haematoxylin-eosin (HE) staining of the liver was performed. We applied an integrated metabolomic and enzyme gene expression analysis to investigate liver metabolic changes, and the gene expression of related metabolic enzymes was determined by real-time PCR and ELISA. Results: OP in blood serum was increased after OP exposure, while body weights of mice were unchanged. Liver weight and its organ coefficient were decreased significantly in the OP (1 μg/kg/day) group, but ALT and AST, as well as the HE staining results, were unchanged after OP treatment. The levels of cytidine, uridine, purine and N-acetylglutamine were increased significantly, and the level of vitamin B6 was decreased significantly in mice treated with OP (1 μg/kg/day). The mRNA and protein levels of Cda and Shmt1 were both increased significantly in OP (1 μg/kg/day)-treated mice. Conclusions: Through metabolomic analysis, our study firstly found that pyrimidine and purine synthesis were promoted and that N-acetylglutamine was upregulated after low-dose OP treatment, indicating that the treatment disturbed nucleic acid and amino acid metabolism in mice liver. View Full-Text
Keywords: metabolomics; 4-tert-octylphenol; low-dose; liver toxicity metabolomics; 4-tert-octylphenol; low-dose; liver toxicity
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Zhou, K.; Ding, X.; Yang, J.; Hu, Y.; Song, Y.; Chen, M.; Sun, R.; Dong, T.; Xu, B.; Han, X.; Wu, K.; Zhang, X.; Wang, X.; Xia, Y. Metabolomics Reveals Metabolic Changes Caused by Low-Dose 4-Tert-Octylphenol in Mice Liver. Int. J. Environ. Res. Public Health 2018, 15, 2686.

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