title: Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach.
abstract: Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Nanyang
authors.initials: N
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Si
authors.initials: S
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Meiying
authors.initials: M
authors.lastname: Li
authors.affiliation: Laboratory of Immunology and Reproductive Biology, School of Medicine, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Kan
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
authors.forename: Ling
authors.initials: L
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China.|Department of Biomedical Veterinary Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada.|School of Biology Sciences, University of Hong Kong, Hong Kong, SAR, China.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D001835:Body Weight; D001923:Brain Chemistry / Q000187:drug effects*; D002210:Caprylates / Q000494:pharmacology* / Q000633:toxicity; D004785:Environmental Pollutants / Q000494:pharmacology* / Q000633:toxicity; D005466:Fluorocarbons / Q000494:pharmacology* / Q000633:toxicity; D057166:High-Throughput Screening Assays / Q000379:methods*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D018377:Neurotransmitter Agents / Q000378:metabolism; D009928:Organ Specificity
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D018377:Neurotransmitter Agents; C023036:perfluorooctanoic acid