In vitro interactions betwen pyridinium aldoximes and endogenous bio-scavenger butyrylcholinesterase in tabun poisoning (CROSBI ID 528966)
Prilog sa skupa u časopisu | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Čalić, Maja ; Kovarik, Zrinka
engleski
In vitro interactions betwen pyridinium aldoximes and endogenous bio-scavenger butyrylcholinesterase in tabun poisoning
Kinetic parameters were evaluated for inhibition and reactivation of tabun-inhibited human plasma butyrylcholinesterase (BChE ; EC 3.1.1.8) by five pyridinium aldoximes: K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide], K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide], K033 [1, 4-bis(2-hydroxyiminomethylpyridinium) butane dibromide], HI-6 [(1-(2’ -hydroxyimi-nomethyl-1'-pyridinium)-3-(4''-carbamoyl-1''-pyridinium)-2-oxapropane dichloride)] and TMB-4 [1, 3-bis(4-hydroxyiminomethylpyridinium) propane dibromide]. Selected aldoximes have been recently evaluated as protectors/reactivators of tabun-inhibited human erythrocyte AChE [1]. Since BChE can be considered an endogenous bio-scavenger of anticholinesterase compounds, in order to discuss the possible use of BChE as scavenging agent, and BChE prophylactic properties, we examined aldoxime interactions with BChE. Progressive inhibition by tabun was faster for BChE than for AChE, indicating that BChE would scavenge tabun prior to AChE inhibition [1]. The reactivation of tabun-inhibited BChE by selected aldoximes was very slow, reaching maximum of 70%, which means that BChE in combination with the aldoximes investigated cannot be considered as catalytic scavenger of tabun. The overall reactivation rate constants were between 2.2 and 53.6 min-1M-1. Interestingly, the fastest reactivation was achieved by K033, aldoxime with the lowest efficacy for reactivation of tabun-inhibited AChE. The phosphorylated BChE had lower affinities for two potent AChE reactivators, K027 and K048, than phosphorylated AChE, indicating that fast AChE reactivation by these aldoximes would not be obstructed by interactions between BChE and aldoxime [1]. All aldoximes reversibly inhibited BChE and the enzyme-aldoxime dissociation constants ranged between 0.04 and 0.70 mM. However, BChE had lower affinities for aldoximes than AChE (except for TMB-4 for which both enzymes had similar affinity) indicating aldoxime preference for binding to the native AChE [1]. These results imply possible use of the aldoximes as protectors of AChE against phosphorylation by tabun. [1] Čalić, M. et al (2006) Toxicology 219, 85-96.
antidotes; nerve agent; tabun; butyrylcholinesterase
233(2007), 1-3 ; 237-238
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Podaci o prilogu
237-238-x.
2007.
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objavljeno
Podaci o matičnoj publikaciji
Toxicology
Szinicz, Ladislaus ; Reiner, Elsa ; Eyer, Peter
0300-483X
Podaci o skupu
New Strategies in Medical Protection Against Organophosphorus Compounds. Tenth International Medical Chemical Defence Conference (MCDC) 2006
poster
26.04.2007-27.04.2007
München, Njemačka
Povezanost rada
Kemija, Temeljne medicinske znanosti