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 po...

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Bibliographic Details
Published in:Chemico-biological interactions 2010-09, Vol.187 (1), p.287-290
Main Authors: Bajgar, Jiri, Karasova, Jana Zdarova, Kassa, Jiri, Cabal, Jiri, Fusek, Josef, Blaha, Vaclav, Tesarova, Sandra
Format: Article
Language:English
Subjects:
Acetylcholinesterase
Acetylcholinesterase - blood
Acetylcholinesterase - metabolism
Animals
Blood
Brain parts
Central Nervous System - drug effects
Central Nervous System - enzymology
Central Nervous System - metabolism
Cholinesterase Reactivators - administration & dosage
Cholinesterase Reactivators - pharmacology
Diaphragm
Drug Therapy, Combination
Enzyme Activation - drug effects
Female
Organophosphate Poisoning
Organophosphates
Oximes - administration & dosage
Oximes - pharmacology
Pyridinium Compounds - administration & dosage
Pyridinium Compounds - pharmacology
Rat
Rats
Rats, Wistar
Reactivators
Tabun
Trimedoxime - administration & dosage
Trimedoxime - pharmacology
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Summary: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.
ISSN:0009-2797
1872-7786
DOI:10.1016/j.cbi.2010.02.009