Toxicity, pharmacokinetics, and effectiveness of the ortho-chlorinated bispyridinium oxime, K870
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F22%3A50019292" target="_blank" >RIV/62690094:18470/22:50019292 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/60162694:G44__/23:00558178 RIV/00179906:_____/22:10447229
Výsledek na webu
<a href="https://www.sciencedirect.com/science/article/pii/S0278691522004343?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0278691522004343?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.fct.2022.113236" target="_blank" >10.1016/j.fct.2022.113236</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Toxicity, pharmacokinetics, and effectiveness of the ortho-chlorinated bispyridinium oxime, K870
Popis výsledku v původním jazyce
Oxime reactivators are causal antidotes for organophosphate intoxication. Herein, the toxicity, pharmacokinetics, and reactivation effectiveness of o-chlorinated bispyridinium oxime K870 are reported. Oxime K870 was found to have a safe profile at a dose of 30 mg/kg in rats. It exhibited rapid absorption and renal clearance similar to those of other charged oximes after intramuscular administration. Its isoxazole-pyridinium degradation product was identified in vivo. Although it showed some improvement in brain targeting, it was nevertheless rapidly effluxed from the central nervous system. Its reactivation effectiveness was evaluated in rats and mice intoxicated with sarin, tabun, VX, and paraoxon and compared with pralidoxime and asoxime. K870 was found to be less effective in reversing tabun poisoning compared to its parent unchlorinated oxime K203. However, K870 efficiently reactivated blood acetylcholinesterase for all tested organophosphates in rats. In addition, K870 significantly protected against intoxication by all tested organophosphates in mice. For these reasons, oxime K870 seems to have a broader reactivation spectrum against multiple organophosphates. It seems important to properly modulate the oximate forming properties (pK(a)) to obtain more versatile oxime reactivators.
Název v anglickém jazyce
Toxicity, pharmacokinetics, and effectiveness of the ortho-chlorinated bispyridinium oxime, K870
Popis výsledku anglicky
Oxime reactivators are causal antidotes for organophosphate intoxication. Herein, the toxicity, pharmacokinetics, and reactivation effectiveness of o-chlorinated bispyridinium oxime K870 are reported. Oxime K870 was found to have a safe profile at a dose of 30 mg/kg in rats. It exhibited rapid absorption and renal clearance similar to those of other charged oximes after intramuscular administration. Its isoxazole-pyridinium degradation product was identified in vivo. Although it showed some improvement in brain targeting, it was nevertheless rapidly effluxed from the central nervous system. Its reactivation effectiveness was evaluated in rats and mice intoxicated with sarin, tabun, VX, and paraoxon and compared with pralidoxime and asoxime. K870 was found to be less effective in reversing tabun poisoning compared to its parent unchlorinated oxime K203. However, K870 efficiently reactivated blood acetylcholinesterase for all tested organophosphates in rats. In addition, K870 significantly protected against intoxication by all tested organophosphates in mice. For these reasons, oxime K870 seems to have a broader reactivation spectrum against multiple organophosphates. It seems important to properly modulate the oximate forming properties (pK(a)) to obtain more versatile oxime reactivators.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30108 - Toxicology
Návaznosti výsledku
Projekt
<a href="/cs/project/GA21-03000S" target="_blank" >GA21-03000S: Modifikované nukleofily pro reaktivaci cholinesteras inhibovaných organofosforovými sloučeninami</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Food and chemical toxicology
ISSN
0278-6915
e-ISSN
1873-6351
Svazek periodika
167
Číslo periodika v rámci svazku
September
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
10
Strana od-do
"Article Number: 113236"
Kód UT WoS článku
000828006900001
EID výsledku v databázi Scopus
2-s2.0-85133438055