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用于评估有机磷农药亚慢性毒性的小鼠模型

Mouse Model for Assessing the Subchronic Toxicity of Organophosphate Pesticides.

作者信息

Palikov V A, Terekhov S S, Palikova Yu A, Khokhlova O N, Kazakov V A, Dyachenko I A, Panteleev S V, Mokrushina Yu A, Knorre V D, Shamborant O G, Smirnov I V, Gabibov A G

机构信息

Branch of the Institute of Bioorganic Chemistry, Academicians M.M. Shemyakin and Yu.A. Ovchinnikova RAS, Nauki Ave., 6, Pushchino, Moscow region, 142290, Russia.

Institute of Bioorganic Chemistry, Academicians M.M. Shemyakin and Yu.A. Ovchinnikova RAS, Miklukho-Maklaya Str., 16/10, Moscow, 117997, Russia.

出版信息

Acta Naturae. 2018 Oct-Dec;10(4):125-128.

PMID:30713772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6351027/
Abstract

The development of antidotes to organophosphate poisons is an important aspect of modern pharmacology. Recombinant acetylcholinesterase and butyrylcholinesterase are effective DNA-encoded acceptors of organophosphate poisons and, in particular, pesticides. Here, we present the results of a study on the effectiveness of recombinant butyrylcholinesterase (BChE) in modeling organophosphate poisoning caused by oral administration of paraoxon at a dose of 2 mg / kg. The study showed a high activity of BChE as a protective agent for subchronic anticholinesterase poisoning in an model. The administration of BChE in a dose of 20 mg / kg allows one to avoid mortality, and also contributed to rapid recovery after model poisoning.

摘要

有机磷酸酯类毒物解毒剂的研发是现代药理学的一个重要方面。重组乙酰胆碱酯酶和丁酰胆碱酯酶是有机磷酸酯类毒物特别是农药的有效DNA编码受体。在此,我们展示了一项关于重组丁酰胆碱酯酶(BChE)对口服2 mg / kg对氧磷所致有机磷酸酯中毒建模有效性的研究结果。该研究表明,在动物模型中,BChE作为亚慢性抗胆碱酯酶中毒的保护剂具有高活性。给予20 mg / kg剂量的BChE可避免死亡,且有助于模型中毒后快速恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e026/6351027/a67ec19ef0b4/AN20758251-10-4-125-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e026/6351027/161ccdd6ed96/AN20758251-10-4-125-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e026/6351027/c05dbd331e4f/AN20758251-10-4-125-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e026/6351027/a67ec19ef0b4/AN20758251-10-4-125-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e026/6351027/161ccdd6ed96/AN20758251-10-4-125-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e026/6351027/c05dbd331e4f/AN20758251-10-4-125-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e026/6351027/a67ec19ef0b4/AN20758251-10-4-125-g003.jpg

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本文引用的文献

1
In vitro skin decontamination of the organophosphorus pesticide Paraoxon with nanometric cerium oxide CeO.用纳米氧化铈CeO对有机磷农药对氧磷进行体外皮肤去污。
Chem Biol Interact. 2017 Apr 1;267:57-66. doi: 10.1016/j.cbi.2016.04.035. Epub 2016 Apr 26.
2
Chemical Polysialylation and In Vivo Tetramerization Improve Pharmacokinetic Characteristics of Recombinant Human Butyrylcholinesterase-Based Bioscavengers.化学多唾液酸化和体内四聚化改善基于重组人丁酰胆碱酯酶的生物清除剂的药代动力学特性。
Acta Naturae. 2015 Oct-Dec;7(4):136-41.
3
Progress in the development of enzyme-based nerve agent bioscavengers.
基于酶的神经毒剂生物清除剂的研究进展。
Chem Biol Interact. 2013 Dec 5;206(3):536-44. doi: 10.1016/j.cbi.2013.06.012. Epub 2013 Jun 26.
4
Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo.化学多聚唾液酸化人重组丁酰胆碱酯酶体内递送长效神经毒生物清除剂。
Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1243-8. doi: 10.1073/pnas.1211118110. Epub 2013 Jan 7.
5
Pulmonary delivery of an aerosolized recombinant human butyrylcholinesterase pretreatment protects against aerosolized paraoxon in macaques.雾化重组人丁酰胆碱酯酶预处理可通过肺部给药来保护猕猴免受雾化敌百虫的侵害。
Chem Biol Interact. 2013 Mar 25;203(1):167-71. doi: 10.1016/j.cbi.2012.11.004. Epub 2012 Nov 21.
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Strategies for the selection of catalytic antibodies against organophosphorus nerve agents.针对有机磷神经毒剂的催化抗体选择策略。
Chem Biol Interact. 2013 Mar 25;203(1):196-201. doi: 10.1016/j.cbi.2012.10.011. Epub 2012 Nov 2.
7
Reactibodies generated by kinetic selection couple chemical reactivity with favorable protein dynamics.动力学选择产生的反应抗体将化学反应性与有利的蛋白质动力学结合在一起。
Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15954-9. doi: 10.1073/pnas.1108460108. Epub 2011 Sep 6.
8
Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behavior.丁酰胆碱酯酶对有机磷中毒的保护:催化复杂性和滞后行为。
Arch Biochem Biophys. 2010 Feb 15;494(2):107-20. doi: 10.1016/j.abb.2009.12.005. Epub 2009 Dec 11.
9
An evaluation of the inhibition of human butyrylcholinesterase and acetylcholinesterase by the organophosphate chlorpyrifos oxon.对有机磷酸酯毒死蜱氧磷抑制人丁酰胆碱酯酶和乙酰胆碱酯酶的评估。
Toxicol Appl Pharmacol. 2009 Dec 1;241(2):135-42. doi: 10.1016/j.taap.2009.08.014. Epub 2009 Aug 19.
10
Management of acute organophosphorus pesticide poisoning.急性有机磷农药中毒的管理
Lancet. 2008 Feb 16;371(9612):597-607. doi: 10.1016/S0140-6736(07)61202-1.