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Effect of five acetylcholinesterase reactivators on tabun‐intoxicated rats: induction of oxidative stress versus reactivation efficacy
Author(s) -
Pohanka Miroslav,
Karasova Jana Zdarova,
Musilek Kamil,
Kuca Kamil,
Kassa Jiri
Publication year - 2009
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1432
Subject(s) - tabun , chemistry , acetylcholinesterase , butyrylcholinesterase , oxidative stress , pharmacology , aché , potency , antioxidant , cholinesterase , oxime , biochemistry , enzyme , medicine , in vitro
Oxime reactivators HI‐6, obidoxime, trimedoxime, K347 and K628 were investigated as drugs designed for treatment of tabun intoxication. The experiments were performed on rats in order to simulate real conditions. Rats were intoxicated with one LD 50 of tabun and treated with atropine and mentioned reactivators. Activities of erythrocyte acetylcholinesterase (AChE), plasma butyrylcholinesterase (BChE) and brain AChE were measured as markers of reactivation efficacy. An estimation of low molecular weight antioxidant levels using cyclic voltammetry was the second examination parameter. The evaluation of cholinesterases activity showed good reactivation potency of blood AChE and plasma BChE by commercially available obidoxime and newly synthesized K347. The potency of oximes to reactivate brain AChE was lower due to the poor blood–brain barrier penetration of used compounds. Commercially available reactivator HI‐6 and newly synthesized K628 caused oxidative stress measured by cyclic voltammetry as antioxidant level. The oxidative stress provoked by HI‐6 and K628 was found to be significant on probability level P = 0.05. The others reactivators did not affect antioxidant levels. Copyright © 2009 John Wiley & Sons, Ltd.