Kinetic analysis of oxime-assisted reactivation of human, Guinea pig, and rat acetylcholinesterase inhibited by the organophosphorus pesticide metabolite phorate oxon (PHO)

Pesticide Biochemistry and Physiology
Robert A MoyerDavid T Yeung

Abstract

Phorate is a highly toxic agricultural pesticide currently in use throughout the world. Like many other organophosphorus (OP) pesticides, the primary mechanism of the acute toxicity of phorate is acetylcholinesterase (AChE) inhibition mediated by its bioactivated oxon metabolite. AChE reactivation is a critical aspect in the treatment of acute OP intoxication. Unfortunately, very little is currently known about the capacity of various oximes to rescue phorate oxon (PHO)-inhibited AChE. To help fill this knowledge gap, we evaluated the kinetics of inhibition, reactivation, and aging of PHO using recombinant AChE derived from three species (rat, guinea pig and human) commonly utilized to study the toxicity of OP compounds and five oximes that are currently fielded (or have been deemed extremely promising) as anti-OP therapies by various nations around the globe: 2-PAM Cl, HI-6 DMS, obidoxime Cl2, MMB4-DMS, and HLö7 DMS. The inhibition rate constants (ki) for PHO were calculated for AChE derived from each species and found to be low (i.e., 4.8×103 to 1.4×104M-1min-1) compared to many other OPs. Obidoxime Cl2 was the most effective reactivator tested. The aging rate of PHO-inhibited AChE was very slow (limited aging was observed ou...Continue Reading

References

Nov 1, 1979·American Industrial Hygiene Association Journal·R J YoungH E Ayer
Feb 1, 1974·Toxicology and Applied Pharmacology·F R Sidell, W A Groff
Jun 1, 1984·Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes·S K KashyapS K Gupta
Aug 1, 1997·Human & Experimental Toxicology·F WorekP Eyer
Apr 30, 2002·QJM : Monthly Journal of the Association of Physicians·M EddlestonN Buckley
Jul 1, 1961·Biochemical Pharmacology·G L ELLMANR M FEATHER-STONE
Sep 2, 2006·Journal of the Neurological Sciences·Kevin Cannard
Nov 23, 2006·Toxicology and Applied Pharmacology·F WorekH Thiermann
Aug 21, 2007·Lancet·Michael EddlestonAndrew H Dawson
Jun 17, 2008·Chemico-biological Interactions·Chunyuan LuoAshima Saxena
Oct 5, 2013·Chemico-biological Interactions·Horst ThiermannKai Kehe
Jan 9, 2014·Journal of Environmental Health Science & Engineering·Summaiya Z LariNeeta P Thacker
Jul 27, 2015·Bulletin of Environmental Contamination and Toxicology·Ahad Bavili Tabrizi, Ali Abdollahi
Apr 30, 2016·Chemico-biological Interactions·Franz WorekTimo Wille
Jan 1, 2016·Fundamental Toxicological Sciences·Thomas H SniderDavid T Yeung

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