In Vitro Ability of Currently Available Oximes to Reactivate Organophosphate Pesticide-Inhibited Human Acetylcholinesterase and Butyrylcholinesterase

International Journal of Molecular Sciences

Daniel Jun²  Lucie Musilova³  Kamil Musilek¹ 

[1] Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, Hradec Kralove, 50001, Czech Republic; E-Mail:;Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, Hradec Kralove, 500 01, Czech Republic;Hospital Pharmacy, University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove, 500 05, Czech Republic; E-Mail:

关键词: acetylcholinesterase;    butyrylcholinesterase;    in vitro;    nerve agent;    organophosphate;    pesticide;    reactivator;    oxime;    scavenger;   

DOI  :  10.3390/ijms12032077

来源: mdpi

【 摘 要 】

We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6) to reactivate human acetylcholinesterase (AChE), inhibited by five structurally different organophosphate pesticides and inhibitors (paraoxon, dichlorvos, DFP, leptophos-oxon and methamidophos). We also tested reactivation of human butyrylcholinesterase (BChE) with the aim of finding a potent oxime, suitable to serve as a “pseudocatalytic” bioscavenger in combination with this enzyme. Such a combination could allow an increase of prophylactic and therapeutic efficacy of the administered enzyme. According to our results, the best broad-spectrum AChE reactivators were trimedoxime and obidoxime in the case of paraoxon, leptophos-oxon, and methamidophos-inhibited AChE. Methamidophos and leptophos-oxon were quite easily reactivatable by all tested reactivators. In the case of methamidophos-inhibited AChE, the lower oxime concentration (10⁻⁵ M) had higher reactivation ability than the 10⁻⁴ M concentration. Therefore, we evaluated the reactivation ability of obidoxime in a concentration range of 10⁻³–10⁻⁷ M. The reactivation of methamidophos-inhibited AChE with different obidoxime concentrations resulted in a bell shaped curve with maximum reactivation at 10⁻⁵ M. In the case of BChE, no reactivator exceeded 15% reactivation ability and therefore none of the oximes can be recommended as a candidate for “pseudocatalytic” bioscavengers with BChE.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.