Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan 430056, China; South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-Sen University, Zhuhai 519082, China.
Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan 430056, China; Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G 2G3, Canada.
J Environ Sci (China). 2022 Jul;117:129-140. doi: 10.1016/j.jes.2022.03.042. Epub 2022 Apr 15.
Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) with a widespread presence in drinking water that exhibit much higher cytotoxicity than regulated DBPs. However, the developmental neurotoxicity of HBQs has not been studied in vivo. In this work, we studied the neurotoxicity of HBQs on zebrafish embryos, after exposure to varying concentrations (0-8 µmol/L) of three HBQs, 2,5-dichloro-1,4-benzoquinone (2,5-DCBQ), 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), and 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ) for 4 to 120 hr post fertilization (hpf). HBQ exposure significantly decreased the locomotor activity of larvae, accompanied by significant reduction of neurotransmitters (dopamine and γ-aminobutyric acid) and acetylcholinesterase activity. Furthermore, the expression of genes involved in neuronal morphogenesis (gfap, α1-tubulin, mbp, and syn-2α) were downregulated by 4.4-, 5.2-, 3.0-, and 4.5-fold in the 5 µmol/L 2,5-DCBQ group and 2.0-, 1.6-, 2.1-, and 2.3-fold in the 5 µmol/L 2,5-DBBQ group, respectively. Transcriptomic analysis revealed that HBQ exposure affected the signaling pathways of neural development. This study demonstrates the significant neurotoxicity of HBQs in embryonic zebrafish and provides molecular evidence for understanding the potential mechanisms of HBQ neurotoxicity.
卤代苯醌（HBQs）是新兴的饮用水消毒副产物（DBPs），具有广泛的存在，其细胞毒性比受管制的 DBPs 高得多。然而，HBQs 的发育神经毒性尚未在体内进行研究。在这项工作中，我们研究了暴露于三种 HBQs（2,5-二氯-1,4-苯醌（2,5-DCBQ）、2,6-二氯-1,4-苯醌（2,6-DCBQ）和 2,5-二溴-1,4-苯醌（2,5-DBBQ））的不同浓度（0-8 μmol/L）下，HBQs 对斑马鱼胚胎的神经毒性，暴露时间为受精后 4 至 120 小时（hpf）。HBQ 暴露显著降低了幼虫的运动活性，同时神经递质（多巴胺和γ-氨基丁酸）和乙酰胆碱酯酶活性显著降低。此外，参与神经元形态发生的基因（gfap、α1-微管蛋白、mbp 和 syn-2α）的表达在 5 μmol/L 2,5-DCBQ 组中分别下调了 4.4、5.2、3.0 和 4.5 倍，在 5 μmol/L 2,5-DBBQ 组中分别下调了 2.0、1.6、2.1 和 2.3 倍。转录组分析表明，HBQ 暴露影响了神经发育的信号通路。这项研究证明了 HBQs 在胚胎斑马鱼中的显著神经毒性，并为理解 HBQ 神经毒性的潜在机制提供了分子证据。
