Naslov
In vitro ability of currently available oximes to reactivate pesticide-inhibited human acetylcholinesterase and butyrylcholinesterase

Autori
Musilova, Lucie ; Jun, Daniel ; Kuca, Kamil ; Pohanka, Miroslav ; Katalinić, Maja ; Kovarik, Zrinka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
10th International Meeting on Cholinesterases, Šibenik, Hrvatska, Programme and Abstracts / Kovarik, Zrinka - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2009, 103-103

ISBN
978-953-95551-3-7

Skup
10th International Meeting on Cholinesterases

Mjesto i datum
Šibenik, Hrvatska, 20.09.2009. - 25.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Oximes; Organophosphates; Cholinesterases; Antidote; Bioscavenger

Sažetak
Organophosphates (OPs) are widely used as pesticides (e.g. parathion, methamidophos) in agriculture, as plasticizers and flame retardants (cresyl diphenyl phosphate, triaryl phosphate) in the industry and as toxic chemical warfare agents (nerve agents, e.g. sarin, VX). OP pesticides are known to cause tens of thousands of deaths every year in the whole world. These compounds act as irreversible inhibitors of acetylcholinesterase (AChE ; EC 3.1.1.7) and butyrylcholinesterase (BChE ; EC 3.1.1.8). For the recovery of function of inhibited AChE, antidotes from the group of pyridinium or bispyridinium aldoximes (oximes) are used. Therapeutic efficacy of these compounds depends on their chemical structure and also type of organophosphorus inhibitor. Another approach in prophylaxis and therapy of OPs intoxication is a use of specific enzymes (mostly AChE and BChE) called bioscavengers. These enzymes are able to neutralize the molecule of toxic OPs in the bloodstream before they can reach their natural targets (AChE and BChE). The ability of currently used oxime reactivators – methoxime, pralidoxime, obidoxime, trimedoxime and HI-6 to reactivate AChE inhibited by OP pesticides is summarized. Moreover, we also tested reactivation of inhibited BChE with the aim to find potent oxime, suitable to serve in combination with this enzyme (administered as prophylactic antidote or occurring naturally in blood) as a “ pseudo catalytic” bioscavenger. Reactivation potency was tested by in vitro screening test using two oxime concentrations (100 μ M and 10 μ M). Paraoxon, dichlorvos, diisopropylfluorophosphate (DFP), leptophos-oxon and methamidophos were used as appropriate organophosphate inhibitors. Human erythrocyte hemolyzate and human plasma were used as sources of AChE and BChE. Our results demonstrated that the best broad-spectrum AChE reactivators after 10 minutes of reactivation are obidoxime and trimedoxime, because they reached more than 50 % of reactivation in the case of paraoxon, leptophos-oxon and methamidophos-inhibited AChE. Methamidophos is quite easily reactivable by all reactivators tested. In the case of BChE, no reactivator achieved sufficient reactivation potency and therefore none from the oximes can be recommended as a candidate for “ pseudo catalytic” bioscavenger.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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