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Pregled bibliografske jedinice broj: 390584

Evaluation of oxime K203 as antidote in tabun poisoning


Kovarik, Zrinka; Lucić Vrdoljak, Ana; Berend, Suzana; Katalinić, Maja; Kuča, Kamil; Musilek, Kamil; Radić, Božica
Evaluation of oxime K203 as antidote in tabun poisoning // Arhiv za higijenu rada i toksikologiju, 60 (2009), 1; 19-26 doi:10.2478/10004-1254-60-2009-1890 (međunarodna recenzija, članak, znanstveni)


Naslov
Evaluation of oxime K203 as antidote in tabun poisoning

Autori
Kovarik, Zrinka ; Lucić Vrdoljak, Ana ; Berend, Suzana ; Katalinić, Maja ; Kuča, Kamil ; Musilek, Kamil ; Radić, Božica

Izvornik
Arhiv za higijenu rada i toksikologiju (0004-1254) 60 (2009), 1; 19-26

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Acetylcholinesterase ; bioscavenger ; butyrylcholinesterase ; K048 ; nerve agents ; TMB-4 ; pyridinium oxime

Sažetak
We studied bispyridinium oxime K203 [(E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyimino methylpyridinium)- but-2-ene dibromide] with tabun-inhibited human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro, and its antidotal effect on tabun-poisoned mice and rats in vivo. We compared it with oximes K048 and TMB-4, which have proven the most effi cient oxime antidotes in tabun poisoning by now. Tabun-inhibited AChE was completely reactivated by K203, with the overall reactivation rate constant of 1806 L mol-1 min-1. This means that K203 is a very potent reactivator of tabun-inhibited AChE. In addition, K203 reversibly inhibited AChE (Ki = 0.090 mmol L-1) and BChE (Ki = 0.91 mmol L-1), and exhibited its protective effect against phosphorylation of AChE by tabun in vitro. In vivo, a quarter of the LD50 K203 dose insured survival of all mice after the application of as many as 8 LD50 doses of tabun, which is the highest dosage obtained compared to K048 and TMB-4. Moreover, K203 showed high therapeutic potency in tabun-poisoned rats, preserving cholinesterase activity in rat plasma up to 60 min after poisoning. This therapeutic improvement obtained by K203 in tabun-poisoning places this oxime in the spotlight for further development.

Izvorni jezik
Engleski

Znanstvena područja
Kemija



POVEZANOST RADA


Projekt / tema
022-0222148-2139 - Terapijski učinak novosintetiziranih spojeva pri otrovanju organofosfatima (Ana Lucić Vrdoljak, )
022-0222148-2889 - Interakcije organofosfata, karbamata i određenih liganada s esterazama (Zrinka Kovarik, )

Ustanove
Institut za medicinska istraživanja i medicinu rada, Zagreb

Časopis indeksira:


  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Uključenost u ostale bibliografske baze podataka:


  • Biological Sciences
  • Pollution Abstracts
  • TOXLINE
  • Water Resources Abstracts
  • Animal Science Database
  • GreenFile
  • INIS
  • Veterinary Science Database
  • TEMA


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