scholarly journals Comparative determination of the efficacy of bispyridinium oximes in paraoxon poisoning / Usporedno određivanje učinkovitosti bispiridinijevih oksima pri trovanju paraoksonom

2015 ◽  
Vol 66 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Suzana Žunec ◽  
Božica Radić ◽  
Kamil Kuča ◽  
Kamil Musilek ◽  
Ana Lucić Vrdoljak
Keyword(s):  
Therapeutic Efficacy ◽  
Standard Therapy ◽  
Organophosphorus Compounds ◽  
Nerve Agents ◽  
Therapeutic Efficiency ◽  
Hi 6 ◽  
Comparative Determination

Abstract The inability of standard therapy to provide adequate protection against poisoning by organophosphorus compounds (pesticides and nerve agents) motivated us to search for new, more effective oximes. We investigated the pharmacotoxicological properties of six experimental K-oximes (K027, K033, K048, K074, K075, and K203) in vivo. The therapeutic efficacy of K-oximes (at doses of 5 or 25 % of their LD50) combined with atropine was assessed in paraoxon-poisoned mice and compared with conventionally used oximes HI-6 and TMB-4. The bisoxime K074 was the most toxic (LD50=21.4 mg kg-1) to mice, while monoxime K027 was the least toxic (LD50=672.8 mg kg-1). With the exception of K033, all of the tested K-oximes showed better therapeutic efficiency than HI-6 and TMB-4. K027 and K048 stood out by demonstrating low acute toxicities and ensuring protective indices ranging from 60.0 to 100.0 LD50 of paraoxon. Taking into account that these two oximes showed a similar therapeutic efficacy regardless of the applied doses, our results suggest that K027 and K048 could be antidotes for paraoxon intoxication.

The Reactivating and Therapeutic Efficacy of Oximes to Counteract Russian VX Poisonings

2006 ◽  
Vol 25 (5) ◽  
pp. 397-401 ◽  
Author(s):  
Jiri Kassa ◽  
Daniel Jun ◽  
Kamil Kuca
Keyword(s):  
Therapeutic Efficacy ◽  
Central Compartment ◽  
Toxic Effects ◽  
Peripheral Compartment ◽  
Structural Analogue ◽  
Hi 6 ◽  
Alkyl Groups ◽  
Brain Acetylcholinesterase ◽  
Acute Toxic

Russian VX ( O-isobutyl- S-(2-diethylaminoethyl)methylphosphonothioate) is the structural analogue of VX agent. It differs from VX agent ( O-ethyl- S-(2-diisopropylaminoethyl) methylphosphonothioate) by two alkyl groups. The potency of currently available oximes (pralidoxime, obidoxime, HI-6) to reactivate Russian VX–inhibited acetylcholinesterase and to eliminate Russian VX–induced acute toxic effects was evaluated using in vivo methods. In vivo determined percentage of reactivation of Russian VX–inhibited blood and brain acetylcholinesterase in poisoned rats shows that HI-6 seems to be the most efficacious reactivator of Russian VX–inhibited acetylcholinesterase among currently used oximes in the peripheral compartment, whereas no difference between reactivating efficacy of all tested oximes was observed in the central compartment. The oxime HI-6 was also found to be the most efficacious oxime in the elimination of acute lethal toxic effects in Russian VX–poisoned mice among all studied oximes. Thus, the oxime HI-6 seems to be the most suitable oxime for the antidotal treatment of acute poisonings with Russian VX as in the case of VX, sarin, cyclosarin, and soman poisonings.

scholarly journals Comparative Determination of Xenobiotics Adsorption

2006 ◽  
Vol 6 (3) ◽  
pp. 54-56
Author(s):  
Mirjana Mijanović ◽  
Asija Začiragić
Keyword(s):  
Organophosphorus Pesticides ◽  
Active Charcoal ◽  
Experimental Animals ◽  
Before And After ◽  
Comparative Determination ◽  
Organochlorine And Organophosphorus Pesticides

Xenobiotic solutions of different concentrations were analyzed by TLC method before and after passing trough the column with adsorbent M and compared with adsorption on the active charcoal. The efficiency of adsorption on adsorbent M was higher, compared to active charcoal. The best adsorption, in the value 90 - 100%, have shown certain organochlorine and organophosphorus pesticides, that were dissolved in non-aqueous solvents. Efficiency of adsorbent M was also proven in vivo, when solutions of tested xenobiotics before adsorption have caused death of experimental animals, and after the adsorption on adsorbent M, all treated animals have survived and had just mild symptoms of poisoning.

scholarly journals The Ability of Oxime Mixtures to Increase the Reactivating and Therapeutic Efficacy of Antidotal Treatment of Cyclosarin Poisoning in Rats and Mice

2012 ◽  
Vol 55 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Jiří Kassa ◽  
Jana Zdarová Karasová ◽  
Růžena Pavlíková ◽  
Filip Caisberger ◽  
Jiří Bajgar
Keyword(s):  
Beneficial Effect ◽  
Therapeutic Efficacy ◽  
Acute Poisoning ◽  
Toxic Effects ◽  
Hi 6 ◽  
Rats And Mice

The reactivating and therapeutic efficacy of two combinations of oximes (HI‑6 + trimedoxime and HI‑6 + K203) was compared with the effectiveness of antidotal treatment involving single oxime (HI‑6, trimedoxime, K203) using in vivo methods. In vivo determined percentage of reactivation of cyclosarin‑inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of both combinations of oximes is slightly higher than the reactivating efficacy of the most effective individual oxime in blood, diaphragm as well as in brain. Moreover, both combinations of oximes were found to be slightly more efficacious in the reduction of acute lethal toxic effects in cyclosarin‑poisoned mice than the antidotal treatment involving single oxime. Based on the obtained data, we can conclude that the antidotal treatment involving chosen combinations of oximes brings a beneficial effect for its ability to counteract the acute poisoning with cyclosarin.

Nanoscavenger provides long-term prophylactic protection against nerve agents in rodents

2019 ◽  
Vol 11 (473) ◽  
pp. eaau7091 ◽  
Author(s):  
Peng Zhang ◽  
Erik J. Liu ◽  
Caroline Tsao ◽  
Shane A. Kasten ◽  
Michael V. Boeri ◽  
...  
Keyword(s):  
Organophosphorus Compounds ◽  
Pharmacokinetic Profile ◽  
Nerve Agents ◽  
Nerve Agent ◽  
Prophylactic Administration ◽  
Guinea Pig Model ◽  
Effective Drugs ◽  
Scavenging Efficiency

Nerve agents are a class of organophosphorus compounds (OPs) that blocks communication between nerves and organs. Because of their acute neurotoxicity, it is extremely difficult to rescue the victims after exposure. Numerous efforts have been devoted to search for an effective prophylactic nerve agent bioscavenger to prevent the deleterious effects of these compounds. However, low scavenging efficiency, unfavorable pharmacokinetics, and immunological problems have hampered the development of effective drugs. Here, we report the development and testing of a nanoparticle-based nerve agent bioscavenger (nanoscavenger) that showed long-term protection against OP intoxication in rodents. The nanoscavenger, which catalytically breaks down toxic OP compounds, showed a good pharmacokinetic profile and negligible immune response in a rat model of OP intoxication. In vivo administration of the nanoscavenger before or after OP exposure in animal models demonstrated protective and therapeutic efficacy. In a guinea pig model, a single prophylactic administration of the nanoscavenger effectively prevented lethality after multiple sarin exposures over a 1-week period. Our results suggest that the prophylactic administration of the nanoscavenger might be effective in preventing the toxic effects of OP exposure in humans.

A comparison of the efficacy of a new asymmetric bispyridinium oxime BI-6 with presently used oximes and H oximes against sarin by in vitro and in vivo methods

1999 ◽  
Vol 18 (9) ◽  
pp. 560-565 ◽  
Author(s):  
J Kassa ◽  
J Cabal
Keyword(s):  
Therapeutic Efficacy ◽  
Hi 6 ◽  
Hlö 7

1 The reactivating and therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6 (1-/2-hydroxyiminomethylpyridinium/-4-/carbamoylpyridinium/-2-butene dibromide), against organophosphate sarin was compared with presently used oximes (pralidoxime, obidoxime, methoxime) and H oximes (HI-6, HLö-7) by in vitro and in vivo methods. 2 Our results confirm that the new oxime BI-6 is a significantly more efficacious acetylcholinesterase reactivator than currently available pralidoxime and obidoxime but not as effective as H oximes (HI-6, HLö-7) in vitro as well as in vivo. In addition, the oxime BI-6 is able to protect supralethal sarin poisoned rats at human-relevant doses. 3 Our data also suggest that the potency of oximes tested to reactivate sarin-inhibited acetylcholinesterase in vitro closely corresponds to their reactivating efficacy in vivo and their ability to protect rats poisoned with supralethal doses of sarin.

Bispyridinium Oximes As Antidotal Treatment of Cyclosarin Poisoning—In Vitro and In Vivo Testing

2005 ◽  
Vol 24 (6) ◽  
pp. 399-402 ◽  
Author(s):  
Lucie Bartosova ◽  
Kamil Kuca ◽  
Daniel Jun ◽  
Gabriela Kunesova
Keyword(s):  
Rat Brain ◽  
Organophosphorus Compounds ◽  
Brain Homogenate ◽  
Chemical Structures ◽  
Hi 6 ◽  
In Vivo Testing ◽  
Acetylcholinesterase Enzyme ◽  
Enzyme Source

The mechanism of intoxication with organophosphorus compounds, including highly toxic nerve agents and less toxic pesticides, is based on the formation of irreversibly inhibited acetylcholinesterase, which causes cumulation of neuromediator acetylcholine in synaptic clefts and subsequent overstimulation of cholinergic receptors, that is followed by a generalized cholinergic crisis. Nerve agent poisoning is conventionally treated using a combination of a cholinolytic (atropine mostly) to counteract the accumulation of acetylcholine and acetylcholinesterase reactivators (pralidoxime or obidoxime) to reactivate inhibited acetylcholinesterase. In this study of cyclosarin poisoning treatment, oximes of different chemical structures (obidoxime, HI-6, BI-6, and HS-6) were tested in vitro on rat brain acetylcholinesterase (enzyme source: rat brain homogenate), and afterwards, they were tested in vivo in equimolar doses, in mice and rats. The HI-6 oxime appeared to be the most effective oxime in vitro and in vivo.

scholarly journals Optimal Choice of Acetylcholinesterase Reactivators for Antidoral Treatment of Nerve Agent Intoxication

2010 ◽  
Vol 53 (4) ◽  
pp. 207-211 ◽  
Author(s):  
Jiří Bajgar
Keyword(s):  
Nerve Agents ◽  
Nerve Agent ◽  
Optimal Choice ◽  
Simple Type ◽  
Hi 6 ◽  
Acetylcholinesterase Reactivators ◽  
Better Than

The studies dealing with mechanism of organophosphates (OP)/nerve agent action, prophylaxis and treatment of intoxications is a very hot topic at present. Though the research is very intensive, unfortunately, up to now, there is not universal or significantly better reactivator sufficiently effective against all nerve agents/OP when compared with presently available oximes (pralidoxime, methoxime, obidoxime, trimedoxime, HI-6). The use of the most effective reactivator (HI-6) using simple type of autoinjector (e.g. ComboPen) is strictly limited because of decomposition of HI-6 in solution. Thanks to better solubility it is clear that another salt of HI-6 (dimethanesulfonate, HI-6 DMS) is more convenient for the use as antidote against nerve agents in the autoinjector than HI-6 chloride (Cl). It was clearly demonstrated that reactivation potency of HI-6 DMS in comparison with HI-6 Cl in vivo was the same and bioavailability of HI-6 DMS is better than that of HI-6 Cl. Three chambered autoinjector allows administration of all three antidotes (atropine, reactivator, diazepam) simultaneously. Moreover, the content of chambers can be changed according to proposed requirements. Possible way to solve the problem of universal reactivator could be the use of two reactivators. Three chambered autoinjector is an ideal device for this purpose.

scholarly journals Bupivacaine-loaded nanostructured lipid carriers prepared with beeswax, lavender or melaleuca oil: characterization and physico-chemical stability

2019 ◽  
Author(s):  
Gabriela Geronimo ◽  
Eneida de Paula ◽  
Gustavo Henrique Rodrigues da Silva ◽  
Lígia Nunes de Morais Ribeiro
Keyword(s):  
Therapeutic Efficacy ◽  
Nanostructured Lipid Carriers ◽  
Physico Chemical ◽  
In Vivo Tests ◽  
Oil Characterization ◽  
New Applications

Although bupivacaine (BVC) is one of the most widely used anesthetics worldwide, improving its therapeutic efficacy without increasing the clinical doses may open possibilities for new applications for this drug. In this study, we prepared innovative formulations: nanostructured lipid carriers (NLC) functionalized with beeswax, lavender or melaleuca oil in order to increase the anesthetic efficiency of BVC. For this, after preparation and characterization of the NLC by dynamic light scattering and determination of the encapsulation efficiency (% EE), stability was monitored during 12 months. The NLC showed appropriate physical-chemical features, with high %EE and stability. The developed formulations proved to be good candidates to increase the therapeutic efficacy of BVC so that further in vitro and in vivo tests are under course to evaluate their advantages, in comparison to the commercial BVC formulation.

scholarly journals Skin Decontamination with Mineral Cationic Carrier Against Sarin Determined In Vivo

2009 ◽  
Vol 60 (2) ◽  
pp. 173-177 ◽  
Author(s):  
Ante Vučemilović ◽  
Mirko Hadžija ◽  
Ivan Jukić
Keyword(s):  
Ion Exchange ◽  
Chemical Defense ◽  
Therapeutic Efficacy ◽  
Research Team ◽  
Nerve Agents ◽  
Defense Research ◽  
Bioactive Potential ◽  
Skin Decontamination

Skin Decontamination with Mineral Cationic Carrier Against Sarin DeterminedIn VivoOur Institute's nuclear, biological, and chemical defense research team continuously investigates and develops preparations for skin decontamination against nerve agents. In thisin vivostudy, we evaluated skin decontamination efficacy against sarin by a synthetic preparation called Mineral Cationic Carrier (MCC®) with known ion exchange, absorption efficacy and bioactive potential. Mice were treated with increasing doses of sarin applied on their skin, and MCC® was administered immediately after contamination. The results showed that decontamination with MCC® could achieve therapeutic efficacy corresponding to 3 x LD50of percutaneous sarin and call for further research.

Sign in / Sign up

Export Citation Format

Share Document