Clethodim exposure induces developmental immunotoxicity and neurobehavioral dysfunction in zebrafish embryos

Clethodim exposure induces developmental immunotoxicity and neurobehavioral dysfunction in zebrafish embryos
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烯草酮暴露诱导斑马鱼胚胎发育免疫毒性和神经行为功能障碍

DOI:
10.1016/j.fsi.2018.12.002
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发表时间:
2019-03
影响因子:
4.7
通讯作者:
Lu Huiqiang
Lu Huiqiang
中科院分区:
农林科学2区
文献类型:
--
作者:
Xiong Guanghua;Zou Lufang;Deng Yunyun;Meng Yunlong;Liao Xinjun;Lu Huiqiang

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克霉威是农业上使用最广泛的除草剂之一,但其对水生生物的潜在负面影响仍然知之甚少。本研究从斑马鱼早期胚胎发育、免疫毒性、细胞凋亡和运动行为等方面研究了克洛地姆对斑马鱼的影响。首先,Clthodim暴露显著降低斑马鱼幼体的存活率、体长和心率,并导致一系列形态异常,主要是脊椎畸形(SD)和卵黄囊水肿。其次,Clthodim暴露后,免疫细胞数量显著减少,而细胞凋亡和氧化应激水平显著增加,且呈剂量依赖关系。第三,我们研究了TLR4、MyD88和NF-κBp65等TLR4、MyD88和NF- μBp65等关键基因在TLR4、MyD88和NF-Bp65中的表达。同时,在模型和TLR4-KD条件下,一些促炎细胞因子如肿瘤坏死因子-α、白介素1-β、白介素8和干扰素-γ也被激活。此外,乙酰胆碱酯酶的运动行为和酶活性明显受到抑制,而乙酰化组蛋白H3的水平则显著增加。此外,将斑马鱼幼体与乙酰胆碱受体(AChR)激动剂卡巴胆碱孵育,可以部分挽救由clthodim调节的运动行为。综上所述,我们的结果表明,氯索地姆具有诱导斑马鱼幼体发育免疫毒性和导致行为改变的潜力。这项研究提供的信息将有助于阐明在水生生态系统中暴露于clthodim的分子机制。
Clethodim is one of the most widely used herbicides in agriculture, but its potential negative effects on aquatic organisms are still poorly understood. This study examined the effects of clethodim on zebrafish at aspects of early stage embryonic development, immune toxicity, cell apoptosis and locomotor behavior. Firstly, clethodim exposure markedly decreased the survival rate, body length, and heart rate and resulted in a series of morphological abnormalities, primarily spinal deformities (SD) and yolk sac edema, in zebrafish larvae. Secondly, the number of immune cells was substantially reduced but the levels of apoptosis and oxidative stress were significantly increased in a dose-dependent manner upon clethodim exposure. Thirdly, we evaluated the expression of some key genes in TLR signaling including TLR4,MyD88, andNF-κB p65and they were all up-regulated by exposure to 300 μg/L clethodim. Meanwhile, some proinflammatory cytokines such asTNF-α,IL-1β,IL8,andIFN-γwere also activated in both the mock and theTLR4-KDconditions. Moreover, the locomotor behaviors and the enzymatic activities of AChE were obviously inhibited but the levels of acetylated histone H3 were greatly increased by clethodim exposure. In addition, incubation of zebrafish larvae with acetylcholine receptor (AChR) agonist carbachol can partially rescue the clethodim-modulated locomotor behavior. Taken together, our results suggest that clethodim has the potential to induce developmental immunotoxicity and cause behavioral alterations in zebrafish larvae. The information presented in this study will help to elucidate the molecular mechanisms underlying clethodim exposure in aquatic ecosystems.
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