Tabun-inhibited rat tissue and blood cholinesterases and their reactivation with the combination of trimedoxime and HI-6 in vivo.
Up to now, intensive attempts to synthesize a universal reactivator able to reactivate cholinesterases inhibited by all types of nerve agents/organophosphates were not successful. Therefore, another approach using a combination of two reactivators differently reactivating enzyme was used: in rats poisoned with tabun and treated with combination of atropine (fixed dose) and different doses of trimedoxime and HI-6, changes of acetylcholinesterase activities (blood, diaphragm and different parts of the brain) were studied. An increase of AChE activity was observed following trimedoxime treatment depending on its dose; HI-6 had very low effect. Combination of both oximes showed potentiation of their reactivation efficacy; this potentiation was expressed for peripheral AChE (blood, diaphragm) and some parts of the brain (pontomedullar area, frontal cortex); AChE in the basal ganglia was relatively resistant. These observations suggest that the action of combination of oximes in vivo is different from that observed in vitro.
Bajgar
Jiri
J
Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic. bajgar@pmfhk.cz
Karasova
Jana Zdarova
JZ
Kassa
Jiri
J
Cabal
Jiri
J
Fusek
Josef
J
Blaha
Vaclav
V
Tesarova
Sandra
S
D000110:Acetylcholinesterase / Q000097:blood* / Q000378:metabolism*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004789:Enzyme Activation / Q000187:drug effects*; D005260:Female; D062025:Organophosphate Poisoning; D010755:Organophosphates; D010091:Oximes / Q000008:administration & dosage / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014289:Trimedoxime / Q000008:administration & dosage / Q000494:pharmacology*
D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D014289:Trimedoxime; D000110:Acetylcholinesterase; C022870:asoxime chloride; C009374:tabun