The benefit of combination of oximes for the neuroprotective efficacy of antidotal treatment of sarin-poisoned rats
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Antidotes administration & dosage therapeutic use MeSH
- Atropine chemistry MeSH
- Chemical Warfare Agents poisoning toxicity MeSH
- Cholinesterase Inhibitors poisoning toxicity MeSH
- Drug Therapy, Combination MeSH
- Rats MeSH
- Molecular Structure MeSH
- Neuroprotective Agents therapeutic use MeSH
- Oximes administration & dosage chemistry therapeutic use MeSH
- Rats, Wistar MeSH
- Pyridinium Compounds administration & dosage chemistry therapeutic use MeSH
- Cholinesterase Reactivators administration & dosage therapeutic use MeSH
- Sarin poisoning toxicity MeSH
- Trimedoxime administration & dosage chemistry therapeutic use MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene MeSH Browser
- Antidotes MeSH
- asoxime chloride MeSH Browser
- Atropine MeSH
- Chemical Warfare Agents MeSH
- Cholinesterase Inhibitors MeSH
- Neuroprotective Agents MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
- Cholinesterase Reactivators MeSH
- Sarin MeSH
- Trimedoxime MeSH
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.
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