The immunotoxicity and neurobehavioral toxicity of zebrafish induced by famoxadone-cymoxanil
The immunotoxicity and neurobehavioral toxicity of zebrafish induced by famoxadone-cymoxanil
复制标题
恶唑菌酮-霜脲氰对斑马鱼的免疫毒性和神经行为毒性
DOI：
10.1016/j.chemosphere.2020.125870
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发表时间：
2020-05-01
期刊：
影响因子：
8.8
通讯作者：
Lu, Huiqiang
中科院分区：
文献类型：
--
作者：
Cheng, Bo;Zhang, Hua;Lu, Huiqiang
作为一种新型的保护性和治疗性杀菌剂，法莫沙酮的研究很少，其对水生生物的毒性尚未见报道。在本研究中，将斑点鱼胚胎暴露于不同浓度的法莫沙酮-环氧苯丙胺，条件为10hpf。观察和检测其形态、心率、天然免疫细胞和获得性免疫细胞的发育和功能、氧化应激、细胞凋亡、凋亡相关基因和免疫相关基因的表达、运动行为的变化。我们的研究表明，斑马鱼胚胎在暴露于法莫沙酮-环磷酰胺后，心率减慢，体长缩短，卵黄囊肿胀。其次，先天免疫细胞和获得性免疫细胞数量显著减少，中性粒细胞在损伤部位的迁移和滞留受到抑制，表明法莫沙酮对斑马鱼具有发育毒性和免疫毒性。我们还发现，胚胎的氧化应激相关指标发生了显著变化，细胞凋亡率大幅增加。进一步研究TLR信号通路中TLR4、MYD88和NF-kappa B p65等关键基因的变化，发现这些基因的mRNA表达上调。同时，一些促炎细胞因子如肿瘤坏死因子-α、干扰素-γ、白介素6和白介素1β的mRNA表达也上调。此外，随着暴露浓度的增加，活动、总距离、时间和平均速度均呈下降趋势。乙酰胆碱酯酶(AChE)的绝对转角、弯曲度和酶活性也增加。这些结果表明，法莫沙酮-环氧苯丙胺对斑马鱼幼体具有发育毒性、免疫毒性和神经行为毒性。(C)2020爱思唯尔有限公司。保留所有权利。
As a new protective and therapeutic fungicide, studies on famoxadone-cymoxanil are rare, and its toxicity to aquatic organisms has not been reported. In the present study, zabrafish embryos were exposed to several concentrations of famoxadone-cymoxanil at 10 hpf. Then, the changes of their shape, heart rate, development and function of innate and adaptive immune cells, oxidative stress, apoptosis, the expression of apoptosis-related genes and immune-related genes, the locomotor behavior were observed and detected in acute toxicity of famoxadone-cymoxanil. Our studies showed that, after exposure to famoxadone-cymoxanil, zebrafish embryos had decreased heart rate, shortened body length, swollen yolk sac. Secondly, the number of innate and adaptive immune cells was significantly reduced; and neutrophil migration and retention at the injury area were inhibited, indicating the developmental toxicity and immunotoxicity of famoxadone-cymoxanil on the zebrafish. We also found that the oxidative stress related indicators of embryos were changed significantly, and apoptosis were substantially increased. Further investigation of changes of some key genes in TLR signaling including TLR4, MYD88 and NF-kappa B p65 revealed that the mRNA expression of these genes was up-regulated. Meanwhile, the mRNA expression of some proinflammatory cytokines such as TNF-alpha, IFN-gamma, IL6 and IL-1 beta was also up-regulated. In addition, the activity, the total distance, time and average speed were decreased along with the increase of exposure concentration. The absolute turn angle, sinuosity and the enzymatic activity of acetylcholinesterase (AChE) were also increased. These results suggested that famoxadone-cymoxanil can induce developmental toxicity, immunotoxicity and neurobehavioral toxicity in zebrafish larvae. (C) 2020 Elsevier Ltd. All rights reserved.