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

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.

Onset rate and intensity of signs of organophosphate poisoning related to paraoxon dose and survival in rats

“…poisoning, which is consistent with the data obtained in this study. 18 The LD 50 of paraoxon, when 10 mg/kg of atropine is administered after 1 minute, was 0.91, so the PR of atropine was 2.73, similar to the data in the literature. 19 Atropine is used as an antidote for poisoning with AChE inhibitors.…”

Interaction of Cucurbit[7]uril with Oxime K027, Atropine, and Paraoxon: Risky or Advantageous Delivery System?

“…Neuroprotective effects of atropine, K027, and K027@CB[7] were studied using a functional observatory battery (FOB). FOB is a standardized set of behavioral and neurophysiological observations, which was developed as a non-invasive procedure for detecting gross functional deficits related to the neurotoxic effects of studied compounds [ 22 , 48 ]. The FOB consists of measurements of sensory, motor, and autonomic nervous functions.…”

The benefit of combinations of oximes for the ability of antidotal treatment to counteract sarin-induced brain damage in rats

“…Selected brain sections were fixed in 10% buffered formalin (Kulich, Hradec Kralove, Czech Republic), processed through conventional histological techniques, and stained with hematoxylin and eosin (both Merck, Kenilworth, NJ, USA). The histological changes were scored using a BX-51 microscope (Olympus, Tokyo, Japan) and following semi-quantitative criteria published previously [ 20 ]: no pathology, mild damage: 1–2 neurons with nucleus margination, chromatolysis and/or vacuolar degeneration, moderate damage: ≥ 3 neurons with changes described in (1) and/or ≥ 1 shrunken eosinophilic neurons in 1 nucleus/subregion, severe damage: focal damage or multiple changes described in (2) present in ≥2 nuclei/subregions and/or hemorrhage very severe damage: diffuse damage of the region and/or multiple hemorrhages …”

“…Washed (3 distilled water washes, 1 min each) and dried slides were mounted with DPX (Sigma-Aldrich) in dark. Fluorescent cells were evaluated using a BX-51 microscope (Olympus) with green excitation fluorescence filter and following semi-quantitative criteria published previously [ 20 ]: no fluorescent cells, 1–2 fluorescent cells in 1 nucleus/subregion, ≥ 3 in 1 nucleus/subregion or 1–2 fluorescent cells in ≥2 nuclei/subregions, multiple fluorescent cells in ≥2 nuclei/subregions and/or hemorrhage, diffuse fluorescent positivity and/or multiple hemorrhages …”