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Reversal of OP toxicity by the oxime-assisted reactivation of cholinesterases (CROSBI ID 676233)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija

Kovarik, Zrinka ; Zorbaz, Tamara ; Maček Hrvat, Nikolina ; Čadež, Tena ; Žunec, Suzana ; Zandona, Antonio ; Katalinić, Maja Reversal of OP toxicity by the oxime-assisted reactivation of cholinesterases // Abstract book of the 16th International Symposium on Cholinergic Mechanism. 2019. str. 25-25

Podaci o odgovornosti

Kovarik, Zrinka ; Zorbaz, Tamara ; Maček Hrvat, Nikolina ; Čadež, Tena ; Žunec, Suzana ; Zandona, Antonio ; Katalinić, Maja

engleski

Reversal of OP toxicity by the oxime-assisted reactivation of cholinesterases

Poisoning caused by the nerve agents (NA) calls for immediate treatment, which usually consists of a combined administration of an anticholinergic drug and an aldoxime as the reactivator of acetylcholinesterase (AChE). Newly considered strategies in medical protection against NA focus on the use of exogenously administered butyrylcholinesterase (BChE). The overall idea is to administer such an enzyme in combination with a specific aldoxime, to scavenge NA before it can reach and inhibit synaptic AChE. We demonstrated through a combination of in silico, in vitro, ex vivo, and in vivo results, a feasible approach to the development of an oxime- assisted catalytic bioscavenger of NA based on the efficient reactivation of cholinesterases. Additionally, several novel aldoximes selected as efficient reactivators of NA-inhibited cholinesterases possessed enhanced brain penetration capabilities, and as such present centrally active reactivators. Most of the tested oximes showed metabolic stability in human liver microsomes and did not affect cell viability of SH-SY5Y neuroblastoma and 1321N1 astrocytoma cell lines upon 24-hours treatment. Taken all together our findings offer a platform for further antidote and scavenger development for exposure to organophosphates. Acknowledgments: This work was supported by the Croatian Science Foundation (IP-2018-01-7683 and UIP-2017-05-7260).

acetylcholinesterase ; butyrylcholinesterase ; nerve agents ; antidotes

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Podaci o prilogu

25-25.

2019.

objavljeno

Podaci o matičnoj publikaciji

Abstract book of the 16th International Symposium on Cholinergic Mechanism

Podaci o skupu

16th International Symposium on Cholinergic Mechanism

pozvano predavanje

08.12.2019-12.12.2019

Reẖovot, Izrael

Povezanost rada

Farmacija, Javno zdravstvo i zdravstvena zaštita, Kemija, Temeljne medicinske znanosti