title: The benefit of combinations of oximes for the reactivating and therapeutic efficacy of antidotal treatment of sarin poisoning in rats and mice.
abstract: The influence of the combinations of oximes on the reactivating and therapeutic efficacy of antidotal treament of acute sarin poisoning was evaluated in this study. The ability of two combinations of oximes (HI-6 + trimedoxime and HI-6 + K203) to reactivate sarin-inhibited acetylcholinesterase and reduce acute toxicity of sarin was compared with the reactivating and therapeutic efficacy of antidotal treatment involving single oxime (HI-6, trimedoxime, K203) using in vivo methods. Studies determining percentage of reactivation of sarin-inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of the combination of oximes involving HI-6 and K203 is slightly higher than the reactivating efficacy of the most effective individual oxime in diaphragm and brain but the difference between them is not significant. The ability of combination of oximes involving HI-6 and trimedoxime to reactivate sarin-inhibited acetylcholinesterase roughly corresponds to the reactivating effects of the most effective individual oxime in blood as well as tissues. Moreover, both combinations of oximes were found to be as efficacious in the reduction of acute lethal toxic effects in sarin-poisoned mice as the most effective individual oxime. A comparison of reactivating and therapeutic efficacy of individual oximes showed that the oxime HI-6 is markedly more effective than the oxime K203 and trimedoxime. Based on the obtained data, we conclude that the antidotal treatment involving chosen combinations of oximes does not significantly influence the ability of the most effective individual oxime (HI-6) to reactivate sarin-inhibited rat acetylcholinesterase and to reduce acute toxicity of sarin in mice.
authors.affiliation: Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic. kassa@pmfhk.cz
authors.forename: Jiri
authors.initials: J
authors.lastname: Kassa
authors.forename: Jana Zdarova
authors.initials: JZ
authors.lastname: Karasova
authors.forename: Vendula
authors.initials: V
authors.lastname: Sepsova
authors.forename: Filip
authors.initials: F
authors.lastname: Caisberger
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology; D002619:Chemical Warfare Agents / Q000506:poisoning; D004359:Drug Therapy, Combination; D008297:Male; D051379:Mice; D010091:Oximes / Q000008:administration & dosage / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012524:Sarin / Q000506:poisoning*; D014289:Trimedoxime / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; D000931:Antidotes; D002619:Chemical Warfare Agents; D010091:Oximes; D011726:Pyridinium Compounds; D014289:Trimedoxime; D012524:Sarin; D000110:Acetylcholinesterase; C022870:asoxime chloride