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两种新制备的双吡啶肟(K305、K307)对塔崩中毒大鼠的重活化和神经保护作用评估——与双复磷及肟K203的比较

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.

作者信息

Kassa Jiri, Misik Jan, Hatlapatkova Jana, Zdarova Karasova Jana, Sepsova Vendula, Caisberger Filip, Pejchal Jaroslav

机构信息

Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.

Clinic of Neurology, Faculty Hospital Hradec Kralove, Sokolovska 581, 500 01 Hradec Kralove, Czech Republic.

出版信息

Molecules. 2017 Jul 11;22(7):1152. doi: 10.3390/molecules22071152.

Abstract

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.

摘要

将两种新开发的肟(K305、K307)对塔崩中毒大鼠的保护能力,与肟K203和三甲肟进行比较,以使其免受塔崩诱导的脑乙酰胆碱酯酶抑制、急性神经毒性体征和症状以及脑损伤。评估了所研究的肟与阿托品联合对亚致死剂量塔崩中毒大鼠的复活和神经保护作用。新开发的肟K305的复活效力低于肟K203和三甲肟的复活效力,而肟K307复活脑中被塔崩抑制的乙酰胆碱酯酶(AChE)的能力大致与肟K203的复活效力相当,且与三甲肟相比略低。此外,只有一种新开发的肟(K307)与阿托品联合能够显著降低塔崩诱导的神经毒性,尽管它并未消除所有塔崩诱导的急性神经毒性体征和症状。这些结果与塔崩诱导的脑损伤的组织病理学评估结果相符。因此,新开发的肟不适用于替代治疗急性塔崩中毒时常用的肟(尤其是三甲肟)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c4/6152392/416ff897feaa/molecules-22-01152-g001.jpg

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