Catalytic organophosphorous compounds scavenging by acetylcholinesterase assisted with aldoximes (CROSBI ID 624214)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija
Podaci o odgovornosti
Kovarik, Zrinka
engleski
Catalytic organophosphorous compounds scavenging by acetylcholinesterase assisted with aldoximes
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.
recativation; OP-enzyme conjugates; acetylcholinesterase
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Podaci o prilogu
45-x.
2015.
objavljeno
Podaci o matičnoj publikaciji
Ukić, Šime ; Bolanča, Tomislav
Zagreb: Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI)
978-953-6894-54-3
Podaci o skupu
24. Hrvatski skup kemičara i kemijskih inženjera
pozvano predavanje
21.04.2015-24.04.2015
Zagreb, Hrvatska