BACKGROUND: The aim of our study was to compare the ability of two combinations of oximes (HI-6 + trimedoxime and HI-6 + K203) with atropine to counteract acute sarin-induced brain damage with the efficacy of antidotal treatment involving single oxime (HI-6) and atropin using in vivo methods. METHODS: Brain damage and neuroprotective effects of antidotal treatment were evaluated in rats poisoned with sarin at a sublethal dose (108 μg/kg i.m.; 90% LD50) using histopathological, Fluoro-Jade B and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis 24 h after sarin administration. RESULTS: Both combinations of oximes reduce the number of rats that died before the end of experiment compared to non-treated sarin poisoning and sarin poisoning treated with HI-6 and atropine. In the case of treatment of sarin poisoning with HI-6 in combination with K203, all rats survived till the end of experiment. HI-6 with atropine was able to reduce sarin-induced brain damage, however, both combinations were slightly more effective. CONCLUSIONS: The oxime HI-6 in combination with K203 and atropine seems to be the most effective. Thus, both tested oxime combinations bring a small benefit in elimination of acute sarin-induced brain damage compared to single oxime antidotal therapy.

• Keywords
• FluoraJadeB, HI-6, Histopathology, K203, Rats, Sarin, TUNEL, Trimedoxime,
• MeSH
• Antidotes therapeutic use   MeSH
• Drug Therapy, Combination MeSH
• Neurotoxicity Syndromes drug therapy   MeSH
• Oximes therapeutic use   MeSH
• Rats, Wistar MeSH
• Sarin poisoning   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antidotes MeSH
• Oximes MeSH
• Sarin MeSH

The ability of two newly developed oximes (K305, K307) to protect tabun-poisoned rats from tabun-induced inhibition of brain acetylcholinesterase, acute neurotoxic signs and symptoms and brain damage was compared with that of the oxime K203 and trimedoxime. The reactivating and neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose were evaluated. The reactivating efficacy of a newly developed oxime K305 is lower compared to the reactivating efficacy of the oxime K203 and trimedoxime while the ability of the oxime K307 to reactivate tabun-inhibited acetylcholinesterase (AChE) in the brain roughly corresponds to the reactivating efficacy of the oxime K203 and it is slightly lower compared to trimedoxime. In addition, only one newly developed oxime (K307) combined with atropine was able to markedly decrease tabun-induced neurotoxicity although it did not eliminate all tabun-induced acute neurotoxic signs and symptoms. These results correspond to the histopathological evaluation of tabun-induced brain damage. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes (especially trimedoxime) in the treatment of acute tabun poisonings.

• Keywords
• acetylcholinesterase, functional observational battery, histopathology, neurotoxicity, oximes, rats, tabun,
• MeSH
• Acetylcholinesterase metabolism   MeSH
• Atropine therapeutic use   MeSH
• Chemical Warfare Agents poisoning   MeSH
• Humans MeSH
• Brain drug effects   enzymology   MeSH
• Neuroprotective Agents therapeutic use   MeSH
• Neurotoxicity Syndromes drug therapy   MeSH
• Organophosphates toxicity   MeSH
• Organophosphate Poisoning drug therapy   MeSH
• Oximes therapeutic use   MeSH
• Rats, Wistar MeSH
• Pyridinium Compounds therapeutic use   MeSH
• Cholinesterase Reactivators therapeutic use   MeSH
• Trimedoxime therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Acetylcholinesterase MeSH
• Atropine MeSH
• Chemical Warfare Agents MeSH
• Neuroprotective Agents MeSH
• Organophosphates MeSH
• Oximes MeSH
• Pyridinium Compounds MeSH
• Cholinesterase Reactivators MeSH
• tabun MeSH Browser
• Trimedoxime MeSH