A Synthetic Receptor as a Specific Antidote for Paraquat Poisoning

Theranostics
Xiangjun ZhangRuibing Wang

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-vivo mice 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 indica...Continue Reading

Citations

May 22, 2019·Organic & Biomolecular Chemistry·Weijian XueLyle Isaacs
Mar 18, 2020·Chemical Society Reviews·Wen-Chao GengDong-Sheng Guo
Oct 2, 2019·Frontiers in Chemistry·Debapratim DasWerner M Nau
Oct 13, 2020·Chemical Society Reviews·Chun-Lin DengLyle D Isaacs
Nov 19, 2020·Chemistry : a European Journal·Steven MurkliLyle Isaacs
Oct 30, 2020·International Journal of Molecular Sciences·Jana Zdarova KarasovaVit Sestak
Apr 16, 2021·Scientific Reports·Fatemeh AminMohammad Hossein Boskabady
Apr 30, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Xin HuangYueyue Chen
Jan 1, 2020·New Journal of Chemistry = Nouveau Journal De Chimie·Sandra Zebaze NdendjioLyle Isaacs
May 4, 2021·Frontiers in Chemistry·Na'il SalehWerner M Nau
May 11, 2021·Frontiers in Pharmacology·Yanxia GaoDing Yuan
Jul 4, 2019·Journal of Agricultural and Food Chemistry·Xiangjun ZhangRuibing Wang
Oct 7, 2021·Chemistry : a European Journal·Adam T BrockettLyle Isaacs

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