Int. J. Mol. Sci. 2011, 12(3), 2077-2087; doi:10.3390/ijms12032077
Article

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

1 Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, Hradec Kralove, 500 01, Czech Republic 2 Department of Water Resources and Environmental Modeling, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamycka 129, Praha 6—Suchdol, 16521, Czech Republic 3 University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove, 50005, Czech Republic 4 Hospital Pharmacy, University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove, 500 05, Czech Republic 5 Department of Biochemical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovskeho 1203, Hradec Kralove, 50005, Czech Republic 6 Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, Hradec Kralove, 50001, Czech Republic
* Authors to whom correspondence should be addressed.
Received: 11 February 2011; Accepted: 9 March 2011 / Published: 23 March 2011
(This article belongs to the Section Molecular Toxicology)
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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.
Keywords: acetylcholinesterase; butyrylcholinesterase; in vitro; nerve agent; organophosphate; pesticide; reactivator; oxime; scavenger

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MDPI and ACS Style

Jun, D.; Musilova, L.; Musilek, K.; Kuca, K. In Vitro Ability of Currently Available Oximes to Reactivate Organophosphate Pesticide-Inhibited Human Acetylcholinesterase and Butyrylcholinesterase. Int. J. Mol. Sci. 2011, 12, 2077-2087.

AMA Style

Jun D, Musilova L, Musilek K, Kuca K. In Vitro Ability of Currently Available Oximes to Reactivate Organophosphate Pesticide-Inhibited Human Acetylcholinesterase and Butyrylcholinesterase. International Journal of Molecular Sciences. 2011; 12(3):2077-2087.

Chicago/Turabian Style

Jun, Daniel; Musilova, Lucie; Musilek, Kamil; Kuca, Kamil. 2011. "In Vitro Ability of Currently Available Oximes to Reactivate Organophosphate Pesticide-Inhibited Human Acetylcholinesterase and Butyrylcholinesterase." Int. J. Mol. Sci. 12, no. 3: 2077-2087.

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