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A Synthetic Receptor as a Specific Antidote for Paraquat Poisoning
Xiangjun Zhang1; Xiaoqiu Xu2; Shengke Li1; Lanlan Li2; Jianxiang Zhang2; Ruibing Wang1
2019
Source PublicationTHERANOSTICS
ISSN1838-7640
Volume9Issue:3Pages:633-645
Abstract

Accidental or suicidal ingestion of the world's most widely used herbicide, paraquat (PQ), may result in rapid multi-organ failure with a 60% fatality rate due to the absence of an effective detoxification solution. Effective, specific antidotes to PQ poisoning have been highly desired.

Methods: The binding constant of PQ and a synthetic receptor, cucurbit[7]uril (CB[7]), was first determined in various pH environments. The antidotal effects of CB[7] on PQ toxicity were firstly evaluated with in-vitro cell lines. With in-vivomice models, the pharmacokinetics and the biodistribution of PQ in major organs were determined to evaluate the influence of CB[7] on the oral bioavailability of PQ. Major organs' injuries and overall survival rates of the mice were systemically examined to evaluate the therapeutic efficacy of CB[7] on PQ poisoning.

Results: We demonstrate that CB[7] may complex PQ strongly under various conditions and significantly reduce its toxicity in vitro and in vivo. Oral administration of PQ in the presence of CB[7] in a mouse model significantly decreased PQ levels in the plasma and major organs and alleviated major organs' injuries, when compared to those of mice administered with PQ alone. Further studies indicated that oral administration of CB[7] within 2 h post PQ ingestion significantly increased the survival rates and extended the survival time of the mice, in contrast to the ineffective treatment by activated charcoal, which is commonly recommended for PQ decontamination.

Conclusion: CB[7] may be used as a specific oral antidote for PQ poisoning by strongly binding with PQ and inhibiting its absorption in the gastrointestinal tracts.

KeywordParaquat Toxicity Cucurbit[7]Uril Antidote Detoxification
DOI10.7150/thno.31485
Indexed BySCI
Language英语
WOS Research AreaResearch & Experimental Medicine
WOS SubjectMedicine, Research & Experimental
WOS IDWOS:000457196900002
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorRuibing Wang
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China
2.Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 400038, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Xiangjun Zhang,Xiaoqiu Xu,Shengke Li,et al. A Synthetic Receptor as a Specific Antidote for Paraquat Poisoning[J]. THERANOSTICS,2019,9(3):633-645.
APA Xiangjun Zhang,Xiaoqiu Xu,Shengke Li,Lanlan Li,Jianxiang Zhang,&Ruibing Wang.(2019).A Synthetic Receptor as a Specific Antidote for Paraquat Poisoning.THERANOSTICS,9(3),633-645.
MLA Xiangjun Zhang,et al."A Synthetic Receptor as a Specific Antidote for Paraquat Poisoning".THERANOSTICS 9.3(2019):633-645.
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