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

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

Pregled bibliografske jedinice broj: 1001288

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

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
Reẖovot, Izrael, 2019. str. 25-25 (pozvano predavanje, međunarodna recenzija, sažetak, znanstveni)

CROSBI ID: 1001288 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

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

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

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

Izvornik
Abstract book of the 16th International Symposium on Cholinergic Mechanism / - , 2019, 25-25

Skup
16th International Symposium on Cholinergic Mechanism

Mjesto i datum
Reẖovot, Izrael, 08.12.2019. - 12.12.2019

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
acetylcholinesterase ; butyrylcholinesterase ; nerve agents ; antidotes

Sažetak
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).

Izvorni jezik
Engleski

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

POVEZANOST RADA

Projekti:
HRZZ-UIP-2017-05-7260 - MOLEKULARNI MEHANIZMI TOKSIČNOSTI PROTUOTROVA I POTENCIJALNIH LIJEKOVA (CellToxTargets) (Katalinić, Maja, HRZZ - 2017-05) ( CroRIS)
HRZZ-IP-2018-01-7683 - Analiza interakcija butirilkolinesteraze s novim inhibitorima i reaktivatorima (AnalyseBChE) (Kovarik, Zrinka, HRZZ - 2018-01) ( CroRIS)

Ustanove:
Institut za medicinska istraživanja i medicinu rada, Zagreb

Profili:

Tena Čadež (autor)