Naslov
Catalytic organophosphorous compounds scavenging by acetylcholinesterase assisted with aldoximes

Autori
Kovarik, Zrinka

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

Izvornik
24. hrvatski skup kemičara i kemijskih inženjera, Zagreb, Hrvatska, Knjiga sažetaka / Ukić, Šime ; Bolanča, Tomislav - Zagreb : Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2015

ISBN
978-953-6894-54-3

Skup
24. hrvatski skup kemičara i kemijskih inženjera

Mjesto i datum
Zagreb, Hrvatska, 21.04.2015. - 24.04.2015

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
recativation; OP-enzyme conjugates; acetylcholinesterase

Sažetak
The high toxicity of organophosphorus compounds (OP ; tabun, soman and VX) originates from the irreversible inhibition of acetylcholinesterase (AChE), an essential enzyme in cholinergic neurotransmission. Poisonings that lead to life-threatening toxic manifestations call for immediate treatment, which usually consists of a combined administration of anticholinergic drugs and an aldoxime as the reactivator of AChE. A new approach to reduce the in vivo toxicity of OPs focuses on the use of bioscavengers enzymes that could react with a nerve agent before it inhibits AChE. Butyrylcholinesterase (BChE), naturally present in plasma, the liver, the small intestine, smooth muscles, heart, adipose tissue, and the brain, is considered an endogenous bioscavenger of OP. Due to the limited concentration of BChE in the organism, a stoichiometric reduction of OP is not sufficient. Furthermore, the stoichiometric approach itself has limitations mostly due to the inability of currently applied aldoximes to reactivate tissue AChE efficiently, particularly when it is repeatedly phosphorylated by an excess of OP that remain in circulation upon exposure. Our recent studies have shown that AChE mutagenesis enables aldoximes to substantially accelerate the reactivation of OP-enzyme conjugates. Moreover, the oxime-enzyme assisted hydrolysis of OP has been proven ex vivo and in vivo. The catalytic scavenging of OP in mice improved the therapeutic outcome and resulted in a delayed onset of toxicity symptoms.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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