Naslov
Antidotal efficacy of bispyridinium oximes against nerve agents

Autori
Radić, Božica ; Berend, Suzana ; Lucić Vrdoljak, Ana ; Kukin, Dijana ; Fuchs, Nino ; Kuča, Kamil

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

Izvornik
Toxicology Letters, Abstracts of the XII International Congress of Toxicology / - , 2010

Skup
XII International Congress of Toxicology

Mjesto i datum
Barcelona, Španjolska, 19.07.2010. - 23.07.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Bispyridinium oximes; soman; sarin; tabun; VX; therapy

Sažetak
Pyridinium oximes have been investigated for many years as compounds with a great potential in the treatment of organophosphorus compounds (OP) poisoning including insecticides and nerve agents. Oximes areknownas reactivators of phosphorylated acetylcholinesterase (AChE), and they have beneficial antinicotinic effects in restoring activity of AChE. Atropine is favourable in the management of acute muscarinic signs and symptoms, and in combination with oximes, it is the treatment of choice for organophosphate poisoning. But there is still interest to develop new antidotes, and also to confirm the efficacy of those that are currently available. In this study in mice poisoned by soman, sarin, tabun and VX we tested the efficacy of three bispyridinium para-oximes with similar basic structure (KO27, KO48, K203) but differing in the linker between two pyridinium rings. In all experiments oxime in dose of 25% or 5% of its LD50 together with atropine (10 mg/kg) as therapy was used one minute after intoxication. Currently used oximes HI-6 and TMB-4 were included for comparison. The antidotal efficacy of tested compounds was expressed as protection index (PI) and maximal dose of poison (MDP). Our experiments showed a relatively good efficacy of the tested oximes in sarin, tabun and VX, but lower in soman poisoning. Similar to HI-6 oxime, the best results with tested oximes were obtained in mice poisoned by VX. MDP was from 25 to 40 LD50 of VX, with survival of all experimental animals. Also, oximes K027 and K048 showed good antidotal efficacy of AChE inhibited by tabun. Their low toxicity is as much as beneficial effect in contrast to high toxicity of currently used TMB-4. It seems, that this results are in accordance with known protective and reactivating potential of pyridinium oximes.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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