title: In vitro ability of currently available oximes to reactivate organophosphate pesticide-inhibited human acetylcholinesterase and butyrylcholinesterase.
abstract: 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.
authors.affiliation: Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, Hradec Kralove, 500 01, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Lucie
authors.initials: L
authors.lastname: Musilova
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000378:metabolism; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000378:metabolism; D010091:Oximes / Q000737:chemistry*; D010575:Pesticides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D010575:Pesticides; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase