title: The benefit of combination of oximes for the neuroprotective efficacy of antidotal treatment of sarin-poisoned rats.
abstract: The potency of the oxime HI-6 and two combinations of oximes (HI-6 + trimedoxime, HI-6 + K203) to reduce sarin-induced acute neurotoxic signs and symptoms was evaluated in this study. Sarin-induced neurotoxicity and the neuroprotective effects of atropine alone or in combination with HI-6 alone and HI-6 combined with trimedoxime or K203 in rats poisoned with sarin at a sublethal dose (108 μg/kg i.m.; 90% of LD(50) value) were monitored by a functional observatory battery (FOB) 24 h following sarin administration. The results indicate that both mixtures of oximes combined with atropine were able to survive sarin-poisoned rats 24 h following sarin administration while two non-treated sarin-poisoned rats and one sarin-poisoned rat treated with atropine alone or with atropine in combination with the oxime HI-6 died within 24 h following sarin poisoning. All types of antidotal treatment were able to decrease sarin-induced neurotoxic signs and symptoms but not completely. While atropine alone and atropine in combination with the oxime HI-6 were able to eliminate some sarin-induced neurotoxic signs and symptoms, the neuroprotective efficacy of both combinations of oximes with atropine was slightly higher. Thus, both tested combinations of oximes in combination with atropine bring a small benefit for the neuroprotective efficacy of antidotal treatment of acute sarin poisonings.
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: Gabriela
authors.initials: G
authors.lastname: Kunesova
mesh_terms: D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use; D001285:Atropine / Q000737:chemistry; D002619:Chemical Warfare Agents / Q000506:poisoning / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000506:poisoning / Q000633:toxicity; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D008297:Male; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010091:Oximes / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012524:Sarin / Q000506:poisoning* / Q000633:toxicity; D014289:Trimedoxime / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; D000931:Antidotes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018696:Neuroprotective Agents; D010091:Oximes; D011726:Pyridinium Compounds; D014289:Trimedoxime; D001285:Atropine; D012524:Sarin; C022870:asoxime chloride