Oxidative Stress and Apoptosis in Bisphenol AF-Induced Neurotoxicity in Zebrafish Embryos

摘要

Bisphenol AF (BPAF) is a structural counterpart of bisphenol A that is utilized in the food and beverage industry.The present study investigated the potential mechanisms in BPAF‐induced neurotoxicity in zebrafish embryos. The BPAFconcentrations (0.03, 0.1, 0.3, and 1.0 μM) had no obvious effect on hatching, mortality, and body length of zebrafish larvae,while curved tail and pericardial edema were observed in the 1.0 μM group at 72 and 96 h postfertilization (hpf). Locomotoractivity of the larvae (at 120 hpf) significantly decreased from dark to light but increased from light to dark transitions in BPAFgroups (0.1, 0.3, and 1.0 μM). Acridine orange showed that BPAF significantly increased green fluorescence protein intensity(22.6) in the 1.0 μM group. Consistently, the induced apoptosis significantly up‐regulated caspase 3 at 0.3 μM (1.95‐fold)and 1.0 μM (2.26‐fold) and bax at 0.3 μM (1.60‐fold) and 1.0 μM (1.78‐fold), whereas bcl‐2 expression was significantlydecreased at 0.3 μM (0.72‐fold) and 1.0 μM (0.53‐fold). In addition, increased reactive oxygen species concentrations at0.3 μM (27) and 1.0 μM (61.4) resulted in suppressed superoxide dismutase and catalase activities. Moreover, quantitativepolymerase chain reaction results showed that BPAF (0.3 and 1.0 μM) significantly altered normal dopaminergic signalingwhere dat was up‐regulated, while drd2a and th1 were down‐regulated, in a concentration‐dependent manner. Aberrationsin dopamine‐related genes were congruous with the dysregulations in neurodevelopment genes (sox11b, pax6a, syn2a, androb2). Our findings suggest that BPAF‐evoked oxidative stress and apoptosis could translate into phenotypical behavioraland neurodevelopmental abnormalities.