Reactivation of Human Acetylcholinesterase and Butyrylcholinesterase Inhibited by Leptophos-Oxon with Different Oxime Reactivators in Vitro

Daniel Jun,Kamil Kuca,Pavel Bostik,Young-Sik Jung,Lucie Musilova,Miroslav Pohanka

doi:10.3390/ijms11082856

Abstract

We have evaluated in vitro the potency of 23 oximes to reactivate human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) inhibited by racemic leptophos-oxon (O-[4-bromo-2,5-dichlorophenyl]-O-methyl phenyl-phosphonate), a toxic metabolite of the pesticide leptophos. Compounds were assayed in concentrations of 10 and 100 μM. In case of leptophos-oxon inhibited AChE, the best reactivation potency was achieved with methoxime, trimedoxime, obidoxime and oxime K027. The most potent reactivators of inhibited BChE were K033, obidoxime, K117, bis-3-PA, K075, K074 and K127. The reactivation efficacy of tested oximes was lower in case of leptophos-oxon inhibited BChE.

Highlights

IntroductionOrganophosphorus pesticides (e.g., chlorpyrifos, methamidophos) and nerve agents (e.g., sarin, tabun, VX) are highly toxic compounds for living organisms due to their ability to inhibit the enzymes acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8)
Organophosphorus pesticides and nerve agents are highly toxic compounds for living organisms due to their ability to inhibit the enzymes acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8)
Combinations of BChE with a suitable reactivator could be used as pseudocatalytic scavengers of organophoshorus pesticides or nerve agents [7,8,9]

Summary

Introduction

Organophosphorus pesticides (e.g., chlorpyrifos, methamidophos) and nerve agents (e.g., sarin, tabun, VX) are highly toxic compounds for living organisms due to their ability to inhibit the enzymes acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8). A relatively new approach for prophylaxis against such intoxication is the administration of a suitable scavenger capable of neutralizing organophosphates rapidly after their penetration into the bloodstream of the organism [6]. For these purposes, catalytic (e.g., phosphotriesterase, human paraoxonase) and stoichiometric (AChE, BChE) enzyme scavengers are targets of intensive investigation. We have evaluated the in vitro potency of 23 structurally different reactivators to reactivate human erythrocyte AChE and plasma BChE inhibited by racemic leptophos-oxon (O-[4-bromo-2,5-dichlorophenyl] O-methyl phenylphosphonate).

Experimental Section

Results

Conclusions