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利用元素成像(LA-ICP-MS)技术研究乙酰胆碱酯酶抑制剂奈拉的毒代动力学在斑马鱼胚胎中的应用。

Elemental imaging (LA-ICP-MS) of zebrafish embryos to study the toxicokinetics of the acetylcholinesterase inhibitor naled.

机构信息

Department of Analytical Chemistry, Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318, Leipzig, Germany.

Department of Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318, Leipzig, Germany.

出版信息

Anal Bioanal Chem. 2019 Jan;411(3):617-627. doi: 10.1007/s00216-018-1471-2. Epub 2018 Nov 16.

Abstract

The zebrafish embryo is an important model in ecotoxicology but the spatial distribution of chemicals and the relation to observed effects is not well understood. Quantitative imaging can help to gain insights into the distribution of chemicals in the zebrafish embryo. Laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) is used to quantify the uptake and the uptake kinetics of the bromine (Br) containing organophosphate naled (Dibrom®, dimethyl-1,2-dibromo-2,2-dichloroethylphosphate) and its distribution in zebrafish embryos using Br as the marker element. During exposure, the Br amounts increase in the embryos parallel to the irreversible inhibition of the acetylcholinesterase (AChE). The final amount of Br in the embryo (545 pmol/embryo) corresponds to a 280-fold enrichment of naled from the exposure solution. However, LC-MS/MS analyses showed that the internal concentration of naled remained below the LOD (7.8 fmol/embryo); also the concentration of its known transformation product dichlorvos remained low (0.85 to 2.8 pmol/embryo). These findings indicate the high reactivity and high transformation rate of naled to other products than dichlorvos. C normalized intensity distributions of Br in the zebrafish embryo showed an enrichment of Br in its head region. Kernel density estimates of the LA-ICP-MS data were calculated and outline the high reproducibility between replicated and the shift in the Br distribution during exposure. The Br enrichment indicates a preferential debromination or direct covalent reaction of naled with AChE in this region. Graphical abstract ᅟ.

摘要

斑马鱼胚胎是生态毒理学中的重要模型,但人们对化学物质的空间分布及其与观察到的效应之间的关系还了解甚少。定量成像可以帮助深入了解化学物质在斑马鱼胚胎中的分布。激光烧蚀电感耦合等离子体质谱(LA-ICP-MS)用于量化含溴有机磷农药 naled(二溴磷,二甲基-1,2-二溴-2,2-二氯乙基磷酸酯)的摄取及其作为标记元素在斑马鱼胚胎中的分布。在暴露过程中,随着乙酰胆碱酯酶(AChE)的不可逆抑制,胚胎中的 Br 含量增加。胚胎中最终的 Br 含量(545 pmol/胚胎)相当于 naled 从暴露溶液中 280 倍的富集。然而,LC-MS/MS 分析表明,naled 的内部浓度仍低于检测限(7.8 fmol/胚胎);其已知转化产物敌敌畏的浓度也很低(0.85 至 2.8 pmol/胚胎)。这些发现表明 naled 比敌敌畏具有更高的反应性和更高的转化速率。斑马鱼胚胎中 Br 的 C 归一化强度分布显示 Br 在头部区域的富集。LA-ICP-MS 数据的核密度估计值被计算出来,并概述了在暴露过程中重复测量之间的高重现性以及 Br 分布的变化。Br 的富集表明在该区域中 naled 优先脱溴或与 AChE 发生直接共价反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1860/6338705/4838bc4ad854/216_2018_1471_Figa_HTML.jpg

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