Naslov
Restoring cholinesterase activity by K048 oxime theraphy in tabun poisoned rats
(Restoring cholinesterase activity by K048 oxime therapy in tabun poisoned rats)

Autori
Maček, Nikolina ; Katalinić, Maja ; Kovarik, Zrinka

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

Izvornik
Book of Abstacts of the 10th Congress of the Croatian Society of Biochemistry and Molecular Biology with international participation "The secret life of biomolecules", HDBMB 2010 / Kovarik, Zrinka ; Varljen, Jadranka - Rijeka : Hrvatsko Društvo za Biotehnologiju, 2010

Skup
10th Congress of the Croatian Society of Biochemistry and Molecular Biology with international participation "The secret life of biomolecules", HDBMB 2010

Mjesto i datum
Rijeka, Hrvatska, 15.09.2010. - 18.09.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Cholinesterase; tabun; oxime; K048; in vitro; in vivo; reactivation

Sažetak
In the event of poisoning by organophosphorus compounds (OP), immediate therapeutic treatment usually consists of combined administration of an anticholinergic drug, such as atropine, and an oxime-reactivator of acetylcholinesterase. However, the treatment is very limiting in case of nerve agent tabun poisoning. Since our recent studies on mice showed that oxime 1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide (K048) is very promising as reactivator of tabun-inhibited human erythrocyte acetylcholinesterase and as antidote of tabun poisoned mice, we tested antidotal potency of K048 in tabun-poisoned rats. We measured acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in rat plasma, brain and diaphragm after 0.5, 1, 6 and 24 h long oxime therapy. Significant reactivation potency of oxime K048 in rat plasma was noticed after 30 and 60 min long oxime therapy (oxime + atropine) when AChE activity was in the range of the control group (rats treated with saline only). The efficiency of K048 decreased after 6 h, probably due to the relatively short oxime circulation time in the blood. Interestingly, after 24 h plasma AChE activities of both poisoned and treated rats were high (in the range of the control group). Unlike in plasma, no significant therapeutic effect of K048 was observed on cholinesterase activity in the rat brain, probably due to the limited penetration of the oxime through the blood brain barrier. In diaphragm inhibition of AChE activity by tabun was not complete, and no significant reactivation was achieved. Further, treatment with K048 did not preserve BChE activity in plasma, brain or diaphragm, which is in agreement with the previous K048 in vitro study, showing limited BChE reactivation by K048.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA