双酚F暴露扰乱小鼠肝脏色氨酸及酪氨酸来源神经递质的代谢作用
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1.南京市栖霞疾病预防控制中心;2.南京医科大学;3.南京医科大学第一附属医院

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Bisphenol F exposure disrupts metabolism of tryptophan and tyrosine derived neurotransmitters in mouse liver
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    摘要:

    目的:探讨双酚F(Bisphenol F,BPF)对肝脏中色氨酸及酪氨酸代谢的影响,阐明其代谢稳态扰乱后神经递质的代谢特点。方法:SPF级C57BL/6J小鼠经灌胃给与不同浓度的BPF(40, 400,4000 μg/kg/day),连续灌胃30天,通过超高效液相色谱-串联质谱(Ultra-high-performance liquid chromatography-tandem mass spectrometry, UHPLC-MS/MS)法观察BPF暴露后,小鼠肝脏色氨酸(Tryptophan,TRP)、酪氨酸(Tyrosine,TYR)来源神经递质代谢特点及水平的改变。结果:BPF暴露后引起小鼠肝脏TRP、TYR水平的下降,其中TRP代谢途经的神经递质五羟色胺(5-hydroxytryptamine,5-HT)水平明显下降,相反,犬尿氨酸(Kynurenine,KYN)水平显著上升;TYR代谢途经中,TYR及其代谢产物多巴胺(Dopamine, DA)水平显著下降;其他兴奋性神经递质递质如谷氨酸(glutamate,GLU),γ-氨基丁酸(γ-aminobutyric acid,GABA),天冬氨酸(Aspartic acid,ASP),甘氨酸(glycine,GLY)水平亦明显降低。结论:BPF暴露可抑制TRP,TYR及多条兴奋性神经递质的代谢,促进TRP通路中5-HT向KYN代谢转化,因而对肝脏神经递质代谢的探讨可为BPF持续暴露导致的肝脏性及神经精神性病变提供依据,具有重要的预防意义。

    Abstract:

    Objective: To investigate the effects of bisphenol F (BPF) on the tryptophan and tyrosine-derived neurotransmitter metabolism in the liver, elucidating the metabolic characteristics of the neurotransmitter disturbance elicited by BPF. Methods: The SPF C57BL/6J mice were administrated with different concentrations of BPF (40, 400, 4000 μg/kg/day) by gavage for 30 consecutive days, and the Ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay was used to examine the characteristics and levels of tryptophan (TRP) and tyrosine (TYR)-derived neurotransmitters in the mouse livers after BPF exposure. Results: The levels of TRP and TYR in mouse livers were significantly decreased after BPF exposure, of note, 5-hydroxytryptamine (5-HT) was significantly decreased and reciprocally, kynurine (Kyn), another key metabolite of the TRP metabolic pathway, significantly increased. For the TYR metabolism, TYR and its metabolite dopamine (DA) obviously decreased; meanwhile, other excitatory neurotransmitters such as glutamate (GLU), γ-aminobutyric acid (GABA), aspartic acid (ASP) and glycine (GLY) dramatically decreased. Conclusion: BPF exposure decreases the levels of TRP, TYR and several other excitatory neurotransmitters, therefore, the current study on the metabolism of hepatic neurotransmitters provides novel evidence for the liver and neuropsychiatric diseases caused by continuous exposure to BPF, which shows important preventive value.

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  • 收稿日期:2022-12-29
  • 最后修改日期:2023-06-09
  • 录用日期:2023-08-29
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