The Evaluation of the Reactivating and Neuroprotective Efficacy of Two Newly Prepared Bispyridinium Oximes (K305, K307) in Tabun-Poisoned Rats-A Comparison with Trimedoxime and the Oxime K203

被引:6
|
作者
Kassa, Jiri [1 ]
Misik, Jan [1 ]
Hatlapatkova, Jana [1 ]
Karasova, Jana Zdarova [1 ]
Sepsova, Vendula [1 ]
Caisberger, Filip [1 ,2 ]
Pejchal, Jaroslav [1 ]
机构
[1] Univ Def, Fac Mil Hlth Sci, Dept Toxicol & Mil Pharm, Trebesska 1575, Hradec Kralove 50001, Czech Republic
[2] Fac Hosp Hradec Kralove, Neurol Clin, Sokolovska 581, Hradec Kralove 50001, Czech Republic
来源
MOLECULES | 2017年 / 22卷 / 07期
关键词
tabun; acetylcholinesterase; neurotoxicity; functional observational battery; histopathology oximes; rats; CHEMICAL WARFARE AGENTS; BLOOD-BRAIN-BARRIER; ORGANOPHOSPHORUS COMPOUNDS; PYRIDINIUM OXIMES; ACETYLCHOLINESTERASE REACTIVATORS; CHOLINESTERASE REACTIVATORS; GUINEA-PIGS; HI-6; SARIN; MICE;
D O I
10.3390/molecules22071152
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:16
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