Dose-response modeling of reactivating potency of oximes K027 and K203 against a direct acetylcholinesterase inhibitor in rat erythrocytes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014820" target="_blank" >RIV/62690094:18470/18:50014820 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0278691518306227?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0278691518306227?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.fct.2018.08.065" target="_blank" >10.1016/j.fct.2018.08.065</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Dose-response modeling of reactivating potency of oximes K027 and K203 against a direct acetylcholinesterase inhibitor in rat erythrocytes

Popis výsledku v původním jazyce

Inhibition of acethylcholinesterase (AChE) as a key molecular event induced by organophosphate (OP) pesticides and nerve agents presents a human health concern. In efficacy testing of experimental oximes, potential antidotes in OP poisoning, reactivation of OP-inhibited AChE is used as specific endpoint. However, according to our best knowledge, so far oximes have not been quantitatively evaluated by comprehensive benchmark dose (BMD) approach, that would improve both identification and quantification of the effect and allow more rigorous comparison of efficacies. Thus, we have examined in vivo dose-response relationship for two promising experimental oximes, K203 and K027, concerning reactivation of erythrocyte AChE inhibited by dichlorvos (DDVP). Groups of Wistar rats were treated with six different doses of oximes (i.m) immediately after DDVP challenge (s.c) and AChE was measured 60 min later. Dose-response modeling was done by PROAST software 65.5 (RIVM, The Nederlands). BMD-covariate method resulted in four-parameter model from both exponential and Hill model families as the best estimate of relationship between AChE activity and oxime dose, with potency parameter being oxime-dependent. Oxime K027 was shown to be 1.929-fold more potent considering that 58% increase in AChE activity was achived with the dose BMD58-K027 = 52 mu mol/kg in contrast to BMD58-K203 = 100 mu mol/kg.

Název v anglickém jazyce

Dose-response modeling of reactivating potency of oximes K027 and K203 against a direct acetylcholinesterase inhibitor in rat erythrocytes

Popis výsledku anglicky

Inhibition of acethylcholinesterase (AChE) as a key molecular event induced by organophosphate (OP) pesticides and nerve agents presents a human health concern. In efficacy testing of experimental oximes, potential antidotes in OP poisoning, reactivation of OP-inhibited AChE is used as specific endpoint. However, according to our best knowledge, so far oximes have not been quantitatively evaluated by comprehensive benchmark dose (BMD) approach, that would improve both identification and quantification of the effect and allow more rigorous comparison of efficacies. Thus, we have examined in vivo dose-response relationship for two promising experimental oximes, K203 and K027, concerning reactivation of erythrocyte AChE inhibited by dichlorvos (DDVP). Groups of Wistar rats were treated with six different doses of oximes (i.m) immediately after DDVP challenge (s.c) and AChE was measured 60 min later. Dose-response modeling was done by PROAST software 65.5 (RIVM, The Nederlands). BMD-covariate method resulted in four-parameter model from both exponential and Hill model families as the best estimate of relationship between AChE activity and oxime dose, with potency parameter being oxime-dependent. Oxime K027 was shown to be 1.929-fold more potent considering that 58% increase in AChE activity was achived with the dose BMD58-K027 = 52 mu mol/kg in contrast to BMD58-K203 = 100 mu mol/kg.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/GA18-01734S" target="_blank" >GA18-01734S: Reaktivátory butyrylcholinesterasy pro přípravu pseudo-katalytických scavengerů využitelných při intoxikacích organofosforovými sloučeninami</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Food and chemical toxicology

ISSN

0278-6915

e-ISSN

—

Svazek periodika

121

Číslo periodika v rámci svazku

listopad

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

224-230

Kód UT WoS článku

000449242800023

EID výsledku v databázi Scopus

2-s2.0-85052992924