title: The potential neurotoxicity of emerging tetrabromobisphenol A derivatives based on rat pheochromocytoma cells.
abstract: Tetrabromobisphenol A (TBBPA) can cause diverse adverse effects including neurotoxicity. Emerging TBBPA derivatives, with high structure similarity to the parent compound, are now being concerned. In this study, the potential neurotoxicities of four TBBPA derivatives and their parent compound were studied by cell viability inhibition in rat pheochromocytoma cells (PC12) and the corresponding molecular mechanisms were investigated. The cellular toxicity was correlated with the chemical hydrophobicity. Tetrabromobisphenol A bis(2-hydroxyethyl ether) (TBBPA-BHEE) exhibited the highest cellular toxicity to PC12 due to its lowest hydrophobicity among these 5 tested compounds. Further experiments showed that TBBPA-BHEE disturbed dopamine (DA) secretion and altered acetylcholinesterase (AChE) enzymatic activity in PC12 cells. The molecular mechanism study indicated that TBBPA-BHEE induced cellular toxicity to PC12 cells through ROS-mediated caspase activation to a large extent, which was partially attenuated by the anti-oxidation of Vitamin E. Moreover, in contrast to TBBPA, the occurrence of TBBPA-BHEE toxicity to PC12 was not attributed to activation of mitogen-activated protein kinases (MAPKs) or thyroid hormone (TH) signaling pathway. These findings suggest TBBPA derivatives, especially TBBPA-BHEE, as potential neurotoxins need urgent attention.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Long
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China. Electronic address: zhouqf@rcees.ac.cn.
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
authors.forename: Guibin
authors.initials: G
authors.lastname: Jiang
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000473:pathology*; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D051381:Rats; D013963:Thyroid Hormones
chemical_list: D009498:Neurotoxins; D018377:Neurotransmitter Agents; D011075:Polybrominated Biphenyls; D013963:Thyroid Hormones; D020928:Mitogen-Activated Protein Kinases; D000110:Acetylcholinesterase; C020806:tetrabromobisphenol A; D000109:Acetylcholine; D004298:Dopamine
keywords: Neurotoxicity; PC12; TBBPA derivatives