Fenobucarb (2-sec-butylphenyl methylcarbamate, BPMC) is an extensively used carbamate insecticide. Its developmental neurotoxicity and the underlying mechanisms have not been well investigated. In this study, zebrafish embryos were exposed to various concentrations of BPMC from 6 hpf (hours post fertilization, hpf) to 120 hpf. BPMC induced developmental toxicity with reduced motility in larval zebrafish. The spinal cord neutrophil infiltration, increased ROS production, caspase 3 and 9 activation, central nerve and peripheral motor neuron damage, axon and myelin degeneration were observed in zebrafish treated with BPMC generally in a dose-dependent manner. The expression of eight marker genes for nervous system function or development, namely, a1-tubulin, shha, elavl3, gap43, syn2a, gfap, mbp and manf, was significantly downregulated following BPMC exposure. AChE activity reduction and ache gene expression suppression was also found significantly in BPMC-treated zebrafish. These results indicate that BPMC is highly toxic to zebrafish and that BPMC induces zebrafish developmental neurotoxicity through pathways involved in inflammation, oxidative stress, degeneration and apoptosis.

中文翻译：

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非诺威威引起的斑马鱼发育神经毒性和机制。

Fenobucarb（2-仲丁基苯基甲基氨基甲酸酯，BPMC）是一种广泛使用的氨基甲酸酯杀虫剂。其发育神经毒性及其潜在机制尚未得到很好的研究。在这项研究中，斑马鱼的胚胎暴露于6 hpf（受精后数小时，hpf）至120 hpf的各种浓度的BPMC中。BPMC诱导幼虫斑马鱼的发育毒性并降低了运动能力。在以BPMC处理的斑马鱼中，通常以剂量依赖性方式观察到脊髓中性粒细胞浸润，ROS产生增加，caspase 3和9活化，中枢神经和周围运动神经元损伤，轴突和髓鞘变性。用于神经系统功能或发育的八个标记基因的表达，即a1-微管蛋白，shha，elavl3，gap43，syn2a，gfap，mbp和manf，BPMC暴露后，其显着下调。在经BPMC处理的斑马鱼中，AChE活性降低和ache基因表达抑制也很明显。这些结果表明，BPMC对斑马鱼具有高毒性，并且BPMC通过涉及炎症，氧化应激，变性和凋亡的途径诱导斑马鱼发育神经毒性。