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用于去除吸入铀的螯合剂组合的制备与评估

Preparation and Evaluation of a Combination of Chelating Agents for the Removal of Inhaled Uranium.

作者信息

Li Lintao, Li Runtian, Guo Ruohan, Guo Shuang, Qiao Xuan, Wu Xinru, Han Peng, Sun Yunbo, Zhu Xiaoxia, Wu Zhuona, Gan Hui, Meng Zhiyun, Dou Guifang, Gu Ruolan, Liu Shuchen

机构信息

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.

出版信息

Molecules. 2024 Dec 5;29(23):5759. doi: 10.3390/molecules29235759.

DOI:10.3390/molecules29235759
PMID:39683918
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11643969/
Abstract

Inhalation of aerosolized uranium is recognized as a principal mode of exposure, posing significant risks of damage to the lungs, kidneys, and other vital organs. To enhance nuclide elimination from the body, chelating agents are employed; however, single-component chelators often exhibit limited spectral activity and low effectiveness, resulting in toxicologically relevant concentrations. We have developed a composite chelating agent composed of 3,4,3-Li(1,2-HOPO), DFP, and HEDP in optimized ratios, demonstrating marked improvements in eliminating inhaled uranium. The selection of these components was initially guided by an agarose gel dynamics method, focusing on uranium binding and removal efficacy. Optimization of the formula was conducted through response surface methodology in a cellular model. The compound's ability to enhance survival rates in mice subjected to acute uranium inhalation was confirmed, showing a dose-dependent improvement in survival in severely affected mice. Comparative assessments indicated that this multifaceted chelating agent substantially surpasses the uranium tissue clearance achieved by individual chelating agents.

摘要

吸入雾化铀被认为是主要的暴露途径，会对肺部、肾脏和其他重要器官造成重大损害风险。为了增强体内核素的清除，人们使用螯合剂；然而，单一组分的螯合剂往往表现出有限的光谱活性和低效性，导致产生毒理学相关浓度。我们研发了一种由3,4,3-Li(1,2-HOPO)、二异丙基氟磷酸酯（DFP）和羟乙膦酸（HEDP）按优化比例组成的复合螯合剂，在消除吸入铀方面有显著改善。这些成分的选择最初是通过琼脂糖凝胶动力学方法进行指导的，重点关注铀的结合和去除效果。配方的优化是在细胞模型中通过响应面法进行的。该化合物提高急性吸入铀小鼠存活率的能力得到了证实，在受严重影响的小鼠中显示出剂量依赖性的存活率提高。比较评估表明，这种多方面的螯合剂大大超过了单个螯合剂实现的铀组织清除率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/0783bb5dc716/molecules-29-05759-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/18c4d8615e43/molecules-29-05759-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/b15499f54d58/molecules-29-05759-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/616509592284/molecules-29-05759-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/b5f68daf90a8/molecules-29-05759-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/512925c81b9b/molecules-29-05759-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/15b2bf306346/molecules-29-05759-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/b623e0a9b8da/molecules-29-05759-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/219a7716ff0c/molecules-29-05759-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/0783bb5dc716/molecules-29-05759-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/18c4d8615e43/molecules-29-05759-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/b15499f54d58/molecules-29-05759-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/616509592284/molecules-29-05759-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/b5f68daf90a8/molecules-29-05759-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/512925c81b9b/molecules-29-05759-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/15b2bf306346/molecules-29-05759-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/b623e0a9b8da/molecules-29-05759-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/219a7716ff0c/molecules-29-05759-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb76/11643969/0783bb5dc716/molecules-29-05759-g009.jpg

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本文引用的文献

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Europium(III) Meets Etidronic Acid (HEDP): A Coordination Study Combining Spectroscopic, Spectrometric, and Quantum Chemical Methods.铕（III）与依替膦酸（HEDP）的配位研究：光谱、光谱法和量子化学方法的结合。
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