Crosstalk of cholinergic pathway on thyroid disrupting effects of the insecticide chlorpyrifos in zebrafish (Danio rerio).
Crosstalk of cholinergic pathway on thyroid disrupting effects of the insecticide chlorpyrifos in zebrafish (Danio rerio).
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DOI：
10.1016/j.scitotenv.2020.143769
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
Kun Qiao;Tiantian Hu;Yao Jiang;Jianping Huang;Jingjin Hu;Wenjun Gui;Q. Ye;Shuying Li;
中科院分区：
文献类型：
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作者：
Kun Qiao;Tiantian Hu;Yao Jiang;Jianping Huang;Jingjin Hu;Wenjun Gui;Q. Ye;Shuying Li;
毒死蜱是一种广泛使用的有机磷杀虫剂，在环境中无处不在。然而，对其对非靶生物的内分泌干扰作用关注甚少。本研究采用毒死蜱浓度分别为13和65 μg/L、连续暴露于斑马鱼7和10 d，观察毒死蜱对斑马鱼的神经毒性和甲状腺代谢的影响。根据急性胚胎毒性测定，毒死蜱120 h lc50和lc10分别为1.35 mg/L和0.62 mg/L。13 μg/L毒死蜱对乙酰胆碱酯酶（AChE）有抑制作用，100和1000 μg/L抗胆碱能药物阿托品可逆转乙酰胆碱酯酶抑制作用。在甲状腺激素水平方面，13和65 μg/L毒死蜱在受精后10 dpf (d)诱导游离t3水平升高。采用实时荧光定量PCR （quantitative Real-Time PCR, qRT-PCR）检测7、10条dpf暴露斑马鱼甲状腺相关基因的表达。tshba、thrb、crhb、ttr、tpo、ugt1abandslc5a5 mRNA表达有显著变化。然而，加入阿托品可以部分挽救甲状腺激素和mRNA表达的改变。利用同源性建模和CDOCKER程序对毒死蜱和T3与斑马鱼甲状腺受体β进行分子对接，结果表明毒死蜱与T3的结合能力较弱。因此，我们认为，毒死蜱对斑马鱼甲状腺信号的干扰可能是由发育性神经毒性引起的。
Chlorpyrifos is a widely used organophosphate insecticide and ubiquitously detected in the environment. However, little attention has been paid to its endocrine disrupting effect to non-target organisms. In the present study, zebrafish was exposed to 13 and 65 μg/L of chlorpyrifos for 7 and 10 days to determine the induced neurotoxicity and the alteration of thyroid metabolism. The 120 h LC50and LC10of chlorpyrifos was estimated as 1.35 mg/L and 0.62 mg/L based on the acute embryo toxicity assay, respectively. The acetylcholinesterase (AChE) inhibitory was detected by 13 μg/L chlorpyrifos and could be reversed by the co-exposure of 100 and 1000 μg/L anticholinergic agent atropine. For thyroid hormone level, 13 and 65 μg/L of chlorpyrifos induced increased free T3levels in 10 dpf (days post-fertilization). The expression of thyroid related genes in 7 and 10 dpf exposed zebrafish were measured by the quantitative Real-Time PCR (qRT-PCR) assay. The mRNA expression oftshba,thrb,crhb,ttr,tpo,ugt1abandslc5a5had significant change. However, the alterations of thyroid hormone and mRNA expression could be partly rescued by the addition of atropine. The molecular docking of chlorpyrifos and T3to the thyroid receptor β in zebrafish using homology modelling and CDOCKER procedures shown weaker binding ability of chlorpyrifos compared to T3. Therefore, we concluded that the disturbance of thyroid signaling in zebrafish might arise from the developmental neurotoxicity induced by chlorpyrifos.