Naslov
Pretreatment with pyridinium oximes improves antidotal therapy against tabun poisoning

Autori
Lucić Vrdoljak, Ana ; Čalić, Maja ; Radić, Božica ; Berend, Suzana ; Jun, Daniel ; Kuča, Kamil ; Kovarik, Zrinka

Izvornik
Toxicology (0300-483X) 228 (2006); 41-50

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

Ključne riječi
acetylcholinesterase; antidote; nerve agent; inhibition; reactivation; oxime; antidotal treatment

Sažetak
Oximes K033 [1, 4-bis(2-hydroxyiminomethylpyridinium) butane dibromide] and K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide] were tested as pretreatment drugs in tabun poisoned mice followed by treatment with atropine plus K033, K048, K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide], TMB-4 [1, 3-bis(4-hydroxyiminomethylpyridinium) propane dibromide] and HI-6 [(1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxapropane dichloride)]. Oxime doses of 25% or 5% of its LD50 were used for pretreatment 15 minutes before tabun-poisoning and for treatment one minute after tabun administration to mice. The best therapeutic effect was obtained when oxime K048 (25% of its LD50) was used in both pretreatment and treatment with atropine. This regiment insured survival of all tested animals after the application of 10 LD50 of tabun. In addition, since BChE is considered an endogenous bio-scavenger of anticholinesterase compounds and its interactions with oximes could be masked by AChE interactions, we evaluated kinetic parameters for interactions of tested oximes with native and tabun-inhibited human plasma butyrylcholinesterase (BChE ; EC 3.1.1.8) and compared them with results obtained previously for human erythrocyte acetylcholinesterase (AChE ; EC 3.1.1.7). Progressive inhibition of BChE by tabun was slightly faster than that of AChE. The reactivation of tabun-inhibited BChE by oximes was very slow, and BChE binding affinity for oximes was lower than AChE's. Therefore, BChE could scavenge tabun prior to AChE inhibition, but fast oxime-assisted reactivation of tabun-inhibited AChE or protection of AChE by oxime against inhibition with tabun would not be obstructed by interaction between BChE and oximes.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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