Pregled bibliografske jedinice broj: 1271056
The toxicity of organophosphorus compounds can be reduced by cholinesterase activity
The toxicity of organophosphorus compounds can be reduced by cholinesterase activity // The Toxicologist - Supplement to Toxicological Sciences
Nashville (TN), Sjedinjene Američke Države: Oxford University Press, 2023. str. 151-151 (poster, međunarodna recenzija, sažetak, znanstveni)
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Naslov
The toxicity of organophosphorus compounds can be reduced by cholinesterase activity
Autori
Kovarik, Zrinka ; Kolić, Dora ; Čadež, Tena ; Maček Hrvat, Nikolina
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
The Toxicologist - Supplement to Toxicological Sciences
/ - : Oxford University Press, 2023, 151-151
Skup
62nd Annual Meeting of the Society of Toxicology & ToxExpo
Mjesto i datum
Nashville (TN), Sjedinjene Američke Države, 19.03.2023. - 23.03.2023
Vrsta sudjelovanja
Poster
Vrsta recenzije
Međunarodna recenzija
Ključne riječi
Organophosphorus compounds ; acetylcholinesterase ; oxime ; nerve agent ; reactivation
Sažetak
The main action mechanism of organophosphorus compounds (OP) is the inhibition of acetylcholinesterase (AChE) that causes the accumulation of the neurotransmitter acetylcholine and excessive stimulation of nicotinic and muscarinic receptors in the central and peripheral nervous system, leading to the paralysis of cholinergic synaptic transmission. Although BChE is generally considered as having no natural physiological function, the most likely function for BChE is as backup for AChE and protection of synaptic AChE from man-made and naturally occurring poisons. Both enzymes should be reactivated by strong nucleophiles such as oximes to avoid severe health effects after exposure to OP. However, inhibition and reactivation of both enzymes are fine-tuning chemical processes that depend on the structure of all reactants. Therefore, we evaluated the inhibition of cholinesterase activity with selected OP-herbicides, insecticides and newly scheduled nerve agents as well as reactivation of OP-inhibited AChE and BChE with click chemistry-synthetized oximes. Although several oximes showed reasonable potency in reactivating AChE and BChE conjugated with methylphosphonates, phosphorates and phosphoramidates, a universally superior antidote was not identified. However, our results showed that toxicity of various OP can be reduced by efficient reactivation of phosphylated AChE and BChE. Our findings also offer a valuable and comprehensive platform for further development of antidotes and scavengers against tabun and related phosphoramidate exposures, such as the Novichok series of compounds. This research was supported by the Croatian Science Foundation (IP-2018-01-7683).
Izvorni jezik
Engleski
Znanstvena područja
Kemija, Temeljne medicinske znanosti, Farmacija
POVEZANOST RADA
Projekti:
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
Citiraj ovu publikaciju:
Časopis indeksira:
- Current Contents Connect (CCC)
- Web of Science Core Collection (WoSCC)
- Science Citation Index Expanded (SCI-EXP)
- SCI-EXP, SSCI i/ili A&HCI
- Scopus
- MEDLINE