In view of the wide application of fluoroquinolones (FQs), a group of broad-spectrum synthetic antibacterial agents, and their large ingress into the environment, the toxic effects on non-target organisms caused by FQs have received great attention. In this study, we used zebrafish embryo as a model, measured the general toxic effects of norfloxacin, a commonly used FQs, and investigated the effects of norfloxacin on the neurodevelopment of zebrafish embryos. Our data showed that norfloxacin significantly inhibited the hatching rate of zebrafish embryos, and increased the mortality and malformation rate of the embryos. To discuss the developmental neurotoxicity of norfloxacin, we measured the expression of several stem cell and neuron lineage markers in the zebrafish embryos. We found that norfloxacin exposure inhibited the expression of GFAP (glial cell marker), and enhanced the expression of Sox 2 (stem cell marker) and Eno2 (mature neuron marker). By measuring the level of active Caspase 3 and the expression ratio of Bax to Bcl2, we discovered that norfloxacin induced obvious cell apoptosis in the brain of zebrafish embryos. To explore the mechanism of the developmental neurotoxic effects of norfloxacin, we applied MK-801, a non-competitive NMDA receptors antagonist, to block the actions of NMDA receptors. The results indicated that MK-801 could rescue the upregulated cell apoptosis and disrupted balance of neuro-glial differentiation induced by norfloxacin in the brain of zebrafish embryos. Our results suggest that the activation of NMDA receptors mediates the developmental neurotoxicity of norfloxacin.

中文翻译：

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诺氟沙星暴露对斑马鱼胚胎的神经发育的影响。

鉴于一类广谱合成抗菌剂氟喹诺酮类（FQs）的广泛应用及其向环境中的大量侵入，由FQs引起的对非目标生物的毒性作用已引起广泛关注。在这项研究中，我们以斑马鱼胚胎为模型，测量了常用的FQ诺氟沙星的一般毒性作用，并研究了诺氟沙星对斑马鱼胚胎神经发育的影响。我们的数据表明，诺氟沙星显着抑制斑马鱼胚胎的孵化率，并增加了胚胎的死亡率和畸形率。为了讨论诺氟沙星的发育神经毒性，我们测量了斑马鱼胚胎中几种干细胞和神经元谱系标志物的表达。我们发现诺氟沙星暴露抑制GFAP（神经胶质细胞标志物）的表达，并增强Sox 2（干细胞标志物）和Eno2（成熟神经元标志物）的表达。通过测量活性Caspase 3的水平和Bax对Bcl2的表达比例，我们发现诺氟沙星在斑马鱼胚胎的大脑中诱导了明显的细胞凋亡。为了探索诺氟沙星对神经发育的毒性作用机理，我们应用了非竞争性NMDA受体拮抗剂MK-801来阻断NMDA受体的作用。结果表明，MK-801可以挽救诺氟沙星在斑马鱼胚胎脑中上调细胞凋亡并破坏神经胶质分化的平衡。我们的结果表明，NMDA受体的激活介导了诺氟沙星的发育神经毒性。