Therapeutic and reactivating efficacy of oximes K027 and K203 against a direct acetylcholinesterase inhibitor
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F16%3A10325227" target="_blank" >RIV/00179906:_____/16:10325227 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/62690094:18470/16:50004748
Výsledek na webu
<a href="http://dx.doi.org/10.1016/j.neuro.2016.05.006" target="_blank" >http://dx.doi.org/10.1016/j.neuro.2016.05.006</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.neuro.2016.05.006" target="_blank" >10.1016/j.neuro.2016.05.006</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Therapeutic and reactivating efficacy of oximes K027 and K203 against a direct acetylcholinesterase inhibitor
Popis výsledku v původním jazyce
As oxime-based structures are the only causal antidotes to organophosphate (OP)-inhibited acetylcholinesterase (AChE), the majority of studies on these have been directed towards their synthesis and testing. In this study, experimental bispyridinium oximes K027 and K203, which have shown promising results in the last decade of research, were examined in vivo for their therapeutic and reactivating ability in acute poisoning by the direct AChE-inhibitor dichlorvos (DDVP), used as a dimethyl OP structural model. Additionally, the efficacy of oximes K027 and K203 was compared with the efficacy of four oximes (pralidoxime, trimedoxime, obidoxime and HI-6), already used in efficacy experiments and human medicine. To evaluate therapeutic efficacy, groups of Wistar rats were treated with equitoxic doses of oximes (5% LD50, i.m.) and/or atropine (10 mg/kg, i.m.) immediately after s.c. DDVP challenge (4-6 doses). Using the same antidotal protocol, AChE activity was measured in erythrocytes, diaphragm and brain 60 min after s.c. DDVP exposure (75% LD50). The oxime K027 was the most efficacious in reducing the DDVP induced lethal effect in rats, while the oxime K203 was more efficacious than trimedoxime, pralidoxime and HI-6. Significant reactivation of DDVP inhibited AChE was achieved only with oxime K027 or its combination with atropine in erythocytes and the diaphragm. Moreover, the acute i.m. toxicity of oxime K027 in rats was lower than all other tested oximes. The results of this study support previous studies considering the oxime K027 as a promising experimental oxime structure for further testing against structurally-different OP compounds.
Název v anglickém jazyce
Therapeutic and reactivating efficacy of oximes K027 and K203 against a direct acetylcholinesterase inhibitor
Popis výsledku anglicky
As oxime-based structures are the only causal antidotes to organophosphate (OP)-inhibited acetylcholinesterase (AChE), the majority of studies on these have been directed towards their synthesis and testing. In this study, experimental bispyridinium oximes K027 and K203, which have shown promising results in the last decade of research, were examined in vivo for their therapeutic and reactivating ability in acute poisoning by the direct AChE-inhibitor dichlorvos (DDVP), used as a dimethyl OP structural model. Additionally, the efficacy of oximes K027 and K203 was compared with the efficacy of four oximes (pralidoxime, trimedoxime, obidoxime and HI-6), already used in efficacy experiments and human medicine. To evaluate therapeutic efficacy, groups of Wistar rats were treated with equitoxic doses of oximes (5% LD50, i.m.) and/or atropine (10 mg/kg, i.m.) immediately after s.c. DDVP challenge (4-6 doses). Using the same antidotal protocol, AChE activity was measured in erythrocytes, diaphragm and brain 60 min after s.c. DDVP exposure (75% LD50). The oxime K027 was the most efficacious in reducing the DDVP induced lethal effect in rats, while the oxime K203 was more efficacious than trimedoxime, pralidoxime and HI-6. Significant reactivation of DDVP inhibited AChE was achieved only with oxime K027 or its combination with atropine in erythocytes and the diaphragm. Moreover, the acute i.m. toxicity of oxime K027 in rats was lower than all other tested oximes. The results of this study support previous studies considering the oxime K027 as a promising experimental oxime structure for further testing against structurally-different OP compounds.
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
FR - Farmakologie a lékárnická chemie
OECD FORD obor
—
Návaznosti výsledku
Projekt
<a href="/cs/project/GA15-16701S" target="_blank" >GA15-16701S: Koncept nekvarterních reaktivátorů AChE jakožto antidot otrav organofosfáty - nová naděje či slepá cesta?</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2016
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
NeuroToxicology
ISSN
0161-813X
e-ISSN
—
Svazek periodika
55
Číslo periodika v rámci svazku
July
Stát vydavatele periodika
NL - Nizozemsko
Počet stran výsledku
7
Strana od-do
33-39
Kód UT WoS článku
000380385800005
EID výsledku v databázi Scopus
2-s2.0-84969560264