Abstract Objective: To study the neurotoxicity and mechanisms of tetrabromobisphenol A bis(2-hydroxyetyl) ether(TBBPA-DHEE) on zebrafish. Methods: Zebrafish embryos were randomly divided into five groups: control group, dimethyl sulfoxide(DMSO) group, TBBPA-DHEE exposure groups(0.086, 0.860 and 8.600 mg/L). After exposure for five days, the mortality, hatching rate, malformation rate, heart rate and body length were observed. Behavioral experiments were used to analyze the spontaneous movement of embryos and the swimming distance and cumulative duration of larvae under light and dark stimulation. The activities of superoxide dismutase(SOD) and glutathione peroxidase(GPx), the contents of malondialdehyde, Ca2+ and γ-aminobutyric acid in larvae were detected by the assay kits. The mRNA expressions of calcium signaling pathway were detected by quantitative real-time PCR method. Results: (1) TBBPA-DHEE exposure could greatly increase the mortality and malformation of zebrafish embryos/larval, and inhibit the incubation of embryos. The heart rate and body length were decreased remarkably.(2)TBBPA-DHEE exposure could significantly reduce the number of spontaneous movement of zebrafish embryos; 0.860 and 8.600 mg/L TBBPA-DHEE exposure significantly reduced the swimming distances and cumulative mobile durations under dark condition.(3) TBBPA-DHEE exposure could increase the activities of SOD and GPx and the content of malondialdehyde. The content of Ca2+ has been increased and the content of gamma-aminobutyric acid has been decreased significantly after TBBPA-DHEE exposure.(4) TBBPA-DHEE exposure could significantly upregulate the mRNA expressions of Cacna1ab, Atp2a1, Atp2a1l, Camk1ga, Ppp3ca, Plcd3a and Prkca in calcium signaling pathways. Conclusion: TBBPA-DHEE could induce the neurotoxicity of zebrafish embryos by enhancing the activities of endogenous antioxidant enzymes and inducing the expressions of related mRNA in calcium signaling pathway.
[Key words]Tetrabromobisphenol A derivative; zebrafish embryos; oxidative stress; calcium signaling pathway; neurotoxicity
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