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.