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蓖麻毒素毒代动力学及其在小鼠血清或粪便中免疫-PCR 法的灵敏检测

Ricin toxicokinetics and its sensitive detection in mouse sera or feces using immuno-PCR.

机构信息

Foodborne Contaminants Research Unit, Western Regional Research Center, United States Department of Agriculture, Agricultural Research Service, Albany, California, USA.

出版信息

PLoS One. 2010 Sep 22;5(9):e12858. doi: 10.1371/journal.pone.0012858.

DOI:10.1371/journal.pone.0012858
PMID:20877567
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2943921/
Abstract

BACKGROUND

Ricin (also called RCA-II or RCA(60)), one of the most potent toxins and documented bioweapons, is derived from castor beans of Ricinus communis. Several in vitro methods have been designed for ricin detection in complex food matrices in the event of intentional contamination. Recently, a novel Immuno-PCR (IPCR) assay was developed with a limit of detection of 10 fg/ml in a buffer matrix and about 10-1000-fold greater sensitivity than other methods in various food matrices.

METHODS AND FINDINGS

In order to devise a better diagnostic test for ricin, the IPCR assay was adapted for the detection of ricin in biological samples collected from mice after intoxication. The limit of detection in both mouse sera and feces was as low as 1 pg/ml. Using the mouse intravenous (iv) model for ricin intoxication, a biphasic half-life of ricin, with a rapid t(1/2)α of 4 min and a slower t(1/2)β of 86 min were observed. The molecular biodistribution time for ricin following oral ingestion was estimated using an antibody neutralization assay. Ricin was detected in the blood stream starting at approximately 6-7 h post- oral intoxication. Whole animal histopathological analysis was performed on mice treated orally or systemically with ricin. Severe lesions were observed in the pancreas, spleen and intestinal mesenteric lymph nodes, but no severe pathology in other major organs was observed.

CONCLUSIONS

The determination of in vivo toxicokinetics and pathological effects of ricin following systemic and oral intoxication provide a better understanding of the etiology of intoxication and will help in the future design of more effective diagnostic and therapeutic methods.

摘要

背景

蓖麻毒素(也称为 RCA-II 或 RCA(60))是最有效的毒素之一,也是有记录的生物武器之一,它来源于 Ricinus communis 的蓖麻豆。已经设计了几种体外方法来检测复杂食物基质中的蓄意污染的蓖麻毒素。最近,开发了一种新型免疫聚合酶链反应(IPCR)检测方法,在缓冲基质中的检测限为 10 fg/ml,在各种食物基质中的灵敏度比其他方法高 10-1000 倍。

方法和发现

为了设计更好的蓖麻毒素诊断检测方法,将 IPCR 检测方法适用于从中毒后收集的小鼠的生物样本中检测蓖麻毒素。在小鼠血清和粪便中的检测限低至 1 pg/ml。使用静脉(iv)注射蓖麻毒素的小鼠模型,观察到蓖麻毒素的双相半衰期,快速 t(1/2)α 为 4 分钟,较慢的 t(1/2)β 为 86 分钟。口服摄入后蓖麻毒素的分子生物分布时间使用抗体中和测定法进行估计。在口服中毒后约 6-7 小时,开始在血流中检测到蓖麻毒素。对经口或系统给予蓖麻毒素的小鼠进行全动物组织病理学分析。在胰腺、脾脏和肠肠系膜淋巴结中观察到严重病变,但在其他主要器官中未观察到严重的病理学变化。

结论

确定全身和口服中毒后蓖麻毒素的体内毒代动力学和病理效应,有助于更好地了解中毒的病因,并有助于未来设计更有效的诊断和治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6246/2943921/7a58338f6ea0/pone.0012858.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6246/2943921/79dd5bd29d0b/pone.0012858.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6246/2943921/dbf1feca7603/pone.0012858.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6246/2943921/9881e1788e0d/pone.0012858.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6246/2943921/7a58338f6ea0/pone.0012858.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6246/2943921/79dd5bd29d0b/pone.0012858.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6246/2943921/dbf1feca7603/pone.0012858.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6246/2943921/9881e1788e0d/pone.0012858.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6246/2943921/7a58338f6ea0/pone.0012858.g004.jpg

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