scholarly journals Neuroprotective Effects of Antidotes in Soman-Poisoned Rats

1999 ◽  
Vol 42 (4) ◽  
pp. 127-131 ◽  
Author(s):  
Jiří Kassa ◽  
Marie Koupilová
Keyword(s):  
Motor Activity ◽  
Automatic Measurement ◽  
Nerve Agents ◽  
The Other ◽  
Sublethal Dose ◽  
Neuroprotective Effects ◽  
Hi 6 ◽  
Other Hand ◽  
Functional Observational Battery

1. The neuroprotective effects of antidotes (atropine, obidoxime/atropine mixture, HI-6/atropine mixture) on rats poisoned with soman at a sublethal dose (48 μg/kg i.m.; 60% of LD50 value) were studied. The neurotoxicity was monitored using a functional observational battery (FOB) and an automatic measurement of motor activity. The neurotoxicity of soman was monitored at 24h and 7d following soman poisoning. 2. The results indicate that atropine alone and the oxime HI-6 in combination with atropine seem to be effective antidotal treatment for the elimination of soman-induced neurotoxicity in the case of sublethal poisonings. 3. On the other hand, the combination of obidoxime with atropine appears to be practically ineffective in diminishing neurotoxic soman-induced symptoms. 4. Dealing with neuroprotective effects of antidotes, the oxime HI-6 in combination with atropine seems to be more suitable antidotal mixture than obidoxime in combination with atropine even in the case of sublethal poisoning with nerve agents.

scholarly journals A Comparison of the Potency of Newly Developed Oximes (K347, K628) and Currently Available Oximes (Obidoxime, HI-6) to Counteract Acute Neurotoxic Effects of Tabun in Rats

2010 ◽  
Vol 53 (2) ◽  
pp. 85-91
Author(s):  
Jiří Kassa ◽  
Jana Žďárová Karasová ◽  
Sandra Tesařová ◽  
Kamil Musílek ◽  
Kamil Kuča
Keyword(s):  
Motor Activity ◽  
Automatic Measurement ◽  
Signs And Symptoms ◽  
Sublethal Dose ◽  
Neuroprotective Effects ◽  
Hi 6 ◽  
Neurotoxic Effects ◽  
Acute Neurotoxicity ◽  
Neuroprotective Efficacy ◽  
Functional Observational Battery

The ability of newly developed oximes (K347, K628) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oximes (obidoxime, HI-6) using a functional observational battery. The neuroprotective effects of the oximes studied (K347, K628, obidoxime, HI-6) combined with atropine on rats poisoned with tabun at a sublethal dose (220 μg/kg i.m.; 80 % of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by a functional observational battery and automatic measurement of motor activity at 24 hours following tabun challenge. The results indicate that all tested oximes combined with atropine enable tabun-poisoned rats to survive 24 hours following tabun challenge. Both newly developed oximes (K347, K628) combined with atropine are able to decrease tabun-induced neurotoxicity in the case of sublethal poisonings but they do not eliminate all tabun-induced acute neurotoxic signs and symptoms. Their ability to decrease the tabun-induced acute neurotoxicity is higher than that of the oxime HI-6 and it is slightly slower than the neuroprotective efficacy of obidoxime. As the neuroprotective potency of both newly developed oximes (K347, K628) is not as high as the potency of obidoxime, they are not a suitable replacement for obidoxime for the treatment of acute tabun poisonings.

scholarly journals A Comparison of the Neuroprotective Efficacy of Pharmacological Pretreatment and Antidotal Treatment in Soman-Poisoned Rats

2003 ◽  
Vol 46 (3) ◽  
pp. 101-107 ◽  
Author(s):  
Jiří Kassa ◽  
Gabriela Krejčová ◽  
Ivan Samnaliev
Keyword(s):  
Motor Activity ◽  
Lethal Dose ◽  
Automatic Measurement ◽  
Albino Rats ◽  
Lethal Effects ◽  
Experimental Animals ◽  
Hi 6 ◽  
Neurotoxic Effects ◽  
Neuroprotective Efficacy ◽  
Functional Observational Battery

1. To study the influence of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment (the oxime HI-6 plus atropine) on soman-induced neurotoxicity, male albino rats were poisoned with a lethal dose of soman (54 (g/kg i.m.; 100% of LD50 value) and observed at 24 hours and 7 days following soman challenge. The neurotoxicity of soman was evaluated using a Functional observational battery and an automatic measurement of motor activity. 2. Pharmacological pretreatment as well as antidotal treatment were able to eliminate some of soman-induced neurotoxic effects observed at 24 hours following soman poisoning. The combination of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment was found to be more effective in the elimination of soman-induced neurotoxicity in rats at 24 hours following soman challenge in comparison with the administration of pharmacological pretreatment or antidotal treatment alone. To compare both pharmacological pretreatments, the combination of pyridostigmine with biperiden seems to be more efficacious to eliminate soman-induced signs of neurotoxicity than PANPAL. 3. At 7 days following soman poisoning, the combination of pharmacological pretreatment involving pyridostigmine and biperiden with antidotal treatment was only able to completely eliminate somaninduced neurotoxic signs. 4. Thus, our findings confirm that the combination of pharmacological pretreatment and antidotal treatment is able not only to protect the experimental animals from the lethal effects of soman but also to eliminate most soman-induced signs of neurotoxicity in poisoned rats. The pharmacological pretreatment containing pyridostigmine and biperiden appears to be more efficacious to eliminate soman-induced neurotoxic sings than PANPAL.

scholarly journals Understanding the Interaction Modes and Reactivity of Trimedoxime toward MmAChE Inhibited by Nerve Agents: Theoretical and Experimental Aspects

2020 ◽  
Vol 21 (18) ◽  
pp. 6510
Author(s):  
Alexandre A. de Castro ◽  
Daniel A. Polisel ◽  
Bruna T. L. Pereira ◽  
Elaine F. F. da Cunha ◽  
Kamil Kuca ◽  
...  
Keyword(s):  
Experimental Data ◽  
Mus Musculus ◽  
Active Site ◽  
Theoretical Calculations ◽  
Nerve Agents ◽  
The Other ◽  
Chemical Weapons ◽  
Reactivation Process ◽  
Other Hand

Organophosphorus (OP) compounds are used as both chemical weapons and pesticides. However, these agents are very dangerous and toxic to humans, animals, and the environment. Thus, investigations with reactivators have been deeply developed in order to design new antidotes with better efficiency, as well as a greater spectrum of action in the acetylcholinesterase (AChE) reactivation process. With that in mind, in this work, we investigated the behavior of trimedoxime toward the Mus musculus acetylcholinesterase (MmAChE) inhibited by a range of nerve agents, such as chemical weapons. From experimental assays, reactivation percentages were obtained for the reactivation of different AChE–OP complexes. On the other hand, theoretical calculations were performed to assess the differences in interaction modes and the reactivity of trimedoxime within the AChE active site. Comparing theoretical and experimental data, it is possible to notice that the oxime, in most cases, showed better reactivation percentages at higher concentrations, with the best result for the reactivation of the AChE–VX adduct. From this work, it was revealed that the mechanistic process contributes most to the oxime efficiency than the interaction in the site. In this way, this study is important to better understand the reactivation process through trimedoxime, contributing to the proposal of novel antidotes.

scholarly journals A Comparison of the Neuroprotective Efficacy of Newly Developed Oximes (K156, K203) and Currently Available Oximes (Obidoxime, HI-6) in Cyclosarin-poisoned Rats

2008 ◽  
Vol 51 (4) ◽  
pp. 215-221 ◽  
Author(s):  
Jiří Kassa ◽  
Jana Žďárová Karasová ◽  
Sandra Tesařová ◽  
Kamil Kuča ◽  
Kamil Musílek
Keyword(s):  
Signs And Symptoms ◽  
Neuroprotective Effects ◽  
Hi 6 ◽  
Neuroprotective Efficacy ◽  
Functional Observational Battery

The neuroprotective effects of newly developed oximes (K156, K203) and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with cyclosarin were studied. The cyclosarin-induced neurotoxicity was monitored using a functional observational battery 24 hours after cyclosarin challenge. The results indicate that a newly developed oxime K156 is able to counteract slightly cyclosarin-induced neurotoxicity while another newly developed oxime K203 is completely ineffective in reducing cyclosarin-induced neurotoxic signs and symptoms. The neuroprotective efficacy of K156 is comparable with commonly used obidoxime and oxime HI-6. Thus, none of the newly developed oximes achieves better neuroprotective efficacy than both commonly used oximes. They are therefore not suitable replacements for antidotal treatment of acute poisonings with cyclosarin.

scholarly journals A Comparison of the Neuroprotective and Reactivating Efficacy of a Novel Bispyridinium Oxime K870 with Commonly Used Pralidoxime and the Oxime HI-6 in Tabun-Poisoned Rats

2021 ◽  
Vol 64 (3) ◽  
pp. 145-152
Author(s):  
Jiří Kassa ◽  
Jana Hatlapatková ◽  
Jana Žďárová Karasová ◽  
Vendula Hepnarová ◽  
Filip Caisberger ◽  
...  
Keyword(s):  
Brain Damage ◽  
Acetylcholinesterase Activity ◽  
Sublethal Dose ◽  
Neuroprotective Effects ◽  
Hi 6 ◽  
Histopathological Evaluation ◽  
Acute Neurotoxicity ◽  
Neuroprotective Efficacy ◽  
The Brain

Aim: The comparison of neuroprotective and central reactivating effects of the oxime K870 in combination with atropine with the efficacy of standard antidotal treatment in tabun-poisoned rats. Methods: The neuroprotective effects of antidotal treatment were determined in rats poisoned with tabun at a sublethal dose using a functional observational battery 2 h and 24 h after tabun administration, the tabun-induced brain damage was investigated by the histopathological evaluation and central reactivating effects of oximes was evaluated by the determination of acetylcholinesterase activity in the brain using a standard spectrophotometric method. Results: The central reactivating efficacy of a newly developed oxime K870 roughly corresponds to the central reactivating efficacy of pralidoxime while the ability of the oxime HI-6 to reactivate tabun-inhibited acetylcholinesterase in the brain was negligible. The ability of the oxime K870 to decrease tabun-induced acute neurotoxicity was slightly higher than that of pralidoxime and similar to the oxime HI-6. These results roughly correspond to the histopathological evaluation of tabun-induced brain damage. Conclusion: The newly synthesized oxime K870 is not a suitable replacement for commonly used oximes in the antidotal treatment of acute tabun poisonings because its neuroprotective efficacy is only slightly higher or similar compared to studied currently used oximes.

A comparison of the efficacy of new asymmetric bispyridinium oxime BI-6 with other oximes (obidoxime, HI-6) against soman in rats

1998 ◽  
Vol 17 (6) ◽  
pp. 331-335 ◽  
Author(s):  
J Kassa
Keyword(s):  
The Other ◽  
Hi 6 ◽  
Other Hand

1 The influence of three oximes (obidoxime, HI-6 and the new asymmetric bispyridinium oxime BI-6) in combination with atropine on soman-induced cholinergic and stressogenic effects in rats was studied. 2 The oxime BI-6 produced significantly higher reactivation of soman-inhibited blood and diaphragm cholinesterases than obidoxime. On the other hand, its reactivating effect was not so high as the effect of the oxime HI-6. 3 There were not significant differences in the reactivation of soman-inhibited brain acetycholinesterase among all three oximes tested. 4 The influence of the oxime BI-6 on soman-induced stressogenic effects was greater than the antistressogenic effects of HI-6 or obidoxime at 1 h or 3 h following soman poisoning. 5 These findings confirm that the oxime BI-6 has no definite advantages over HI-6 in the antidotal treatment of soman poisoning but BI-6 is significantly more effective in rats than obidoxime, one of the oximes presently in use.

scholarly journals 1,3–Bis(2–hydroxyiminomethylpyridinium) Propane as the Potential Reactivator of the Acetylcholinesterase Inhibited by Nerve Agents

2004 ◽  
Vol 47 (3) ◽  
pp. 167-169 ◽  
Author(s):  
Kamil Kuča ◽  
Vlastimil Dohnal
Keyword(s):  
Maximum Concentration ◽  
Nerve Agents ◽  
The Other ◽  
Other Hand ◽  
Human Use

The oxime K005 [1,3–bis(2–hydroxyiminomethylpyridinium) propane dibromide] for the reactivation of the enzyme acetylcholinesterase (AChE) inhibited by cyclosarin and VX was tested. Its reactivation potency was not better in comparison with the currently used AChE reactivator – pralidoxime. On the other hand, the oxime K005 has its maximum reactivation ability at the concentration 10–4 M, which could be achieved for human use. The maximum concentration of pralidoxime was reached at the concentrations 10–1 M (for cyclosarin) and 10–3 M (for VX) but these concentrations are not available for the use in vivo.

scholarly journals The Influence of Oxime Selection on the Efficacy of Antidotal Treatment of Soman-Poisoned Rats

2002 ◽  
Vol 45 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Jiří Kassa ◽  
Josef Fusek
Keyword(s):  
Rat Model ◽  
The Other ◽  
Toxic Effects ◽  
Experimental Animals ◽  
Hi 6 ◽  
Other Hand ◽  
On Line ◽  
Acetylcholinesterase Reactivators

1. The influence of some acetylcholinesterase reactivators (HI-6, obidoxime, pralidoxime) on the efficacy of antidotal treatment to eliminate soman-induced disturbance of respiration and circulation and to protect experimental animals poisoned with supralethal dose of soman (1.5 × LD50) was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. 2. Obidoxime or pralidoxime in combination with atropine were insufficient to enable soman-poisoned rats to survive for 2 hours when given 1 minute after the administration of soman. 3. On the other hand, the ability of the oxime HI-6 in combination with atropine to prevent soman-induced alteration of respiration and circulation was significantly higher. Some rats treated with HI-6 in combination with atropine were fully protected against the lethal toxic effects of soman within 2 hours following soman administration. 4. Our findings confirm that the oxime HI-6 seems to be a much more suitable and efficacious acetylcholinesterase reactivator for the antidotal treatment of severe acute soman-induced poisoning than currently used obidoxime or pralidoxime.

scholarly journals The Influence of Anticholinergic Drug Selection on the Effectiveness of Oximes Against Soman-Induced Supralethal Poisoning in Mice

2001 ◽  
Vol 44 (2) ◽  
pp. 77-79 ◽  
Author(s):  
Jiří Kassa
Keyword(s):  
Anticholinergic Drug ◽  
The Other ◽  
Toxic Effects ◽  
Anticholinergic Drugs ◽  
Drug Selection ◽  
Hi 6 ◽  
Prophylactic Administration ◽  
Other Hand ◽  
Selection For

1. The influence of anticholinergic drugs (atropine, benactyzine, biperiden) on the efficacy of monopyridinium and bispyridinium oximes (HI-6, BI-6, obidoxime, pralidoxime, methoxime) on soman-induced supralethal poisoning was studied in mice. 2. While methoxime combined with benactyzine or biperiden seems to be more efficacious in the elimination of toxic effects of supralethal dose of soman than its combination with atropine, the efficacy of the other oximes studied against soman-induced toxic effects is not significantly influenced by the anticholinergic drug selection. 3. On the other hand, there are big differences in the effectiveness of oximes tested as to their ability to eliminate toxic effects of soman at supralethal doses. 4. The findings support the fact that the choice of acetylcholinesterase reactivator is more important than the anticholinergic drug selection for the effectivenes of antidotal mixture in the case of prophylactic administration of antidotes.

scholarly journals A Comparison of the Potency of the Oxime HLö-7 and Currently Used Oximes (HI-6, Pralidoxime, Obidoxime) to Reactivate Nerve Agent-Inhibited Rat Brain Acetylcholinesterase by in vitro Methods

2005 ◽  
Vol 48 (2) ◽  
pp. 81-86 ◽  
Author(s):  
Kamil Kuča ◽  
Jiří Cabal ◽  
Jiří Kassa ◽  
Daniel Jun ◽  
Martina Hrabinová
Keyword(s):  
Rat Brain ◽  
Nerve Agents ◽  
Nerve Agent ◽  
The Other ◽  
In Vitro Evaluation ◽  
In Vitro Methods ◽  
Hi 6 ◽  
Hlö 7 ◽  
Brain Acetylcholinesterase

1. The efficacy of the oxime HLö-7 and currently used oximes (pralidoxime, obidoxime, HI-6) to reactivate acetylcholinesterase inhibited by various nerve agents (sarin, tabun, cyclosarin, VX) was tested by in vitro methods. 2. Both H oximes (HLö-7, HI-6) were found to be more efficacious reactivators of sarin and VX-inhibited acetylcholinesterase than pralidoxime and obidoxime. On the other hand, their potency to reactivate tabun-inhibited acetylcholinesterase is very low and does not reach the reactivating efficacy of obidoxime. In the case of cyclosarin, the oxime HI-6 was only found to be able to sufficiently reactivate cyclosarin-inhibited acetylcholinesterase in vitro. 3. Thus, the oxime HLö-7 does not seem to be more efficacious reactivator of nerve agent-inhibited acetylcholinesterase than HI-6 according to in vitro evaluation of their reactivation potency and, therefore, it is not more suitable to be introduced for antidotal treatment of nerve agent-exposed people than HI-6.

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