Influence of Experimental End Point on the Therapeutic Efficacy of Essential and Additional Antidotes in Organophosphorus Nerve Agent-Intoxicated Mice

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F23%3A00558023" target="_blank" >RIV/60162694:G44__/23:00558023 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mdpi.com/2305-6304/10/4/192" target="_blank" >https://www.mdpi.com/2305-6304/10/4/192</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/toxics10040192" target="_blank" >10.3390/toxics10040192</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Influence of Experimental End Point on the Therapeutic Efficacy of Essential and Additional Antidotes in Organophosphorus Nerve Agent-Intoxicated Mice

Popis výsledku v původním jazyce

The therapeutic efficacy of treatments for acute intoxication with highly toxic organophosphorus compounds, called nerve agents, usually involves determination of LD50 values 24 h after nerve agent challenge without and with a single administration of the treatment. Herein, the LD50 values of four nerve agents (sarin, soman, tabun and cyclosarin) for non-treated and treated in-toxication were investigated in mice for experimental end points of 6 and 24 h. The LD50 values of the nerve agents were evaluated by probit-logarithmical analysis of deaths within 6 and 24 h of i.m. challenge of the nerve agent at five different doses, using six mice per dose. The efficiency of atropine alone or atropine in combination with an oxime was practically the same at 6 and 24 h. The therapeutic efficacy of the higher dose of the antinicotinic compound MB327 was slightly higher at the 6 h end point compared to the 24 h end point for soman and tabun intoxication. A higher dose of MB327 increased the therapeutic efficacy of atropine alone for sarin, soman and tabun intoxication, and that of the standard antidotal treatment (atropine and oxime) for sarin and tabun intoxication. The therapeutic efficacy of MB327 was lower than the oxime-based anti-dotal treatment. To compare the 6 and 24 h end points, the influence of the experimental end point was not observed, with the exception of the higher dose of MB327. In addition, only a neg-ligible beneficial impact of the compound MB327 was observed. Nevertheless, antinicotinics may offer an additional avenue for countering poisoning by nerve agents that are difficult to treat, and synthetic and biological studies towards the development of such novel drugs based on the core bispyridinium structure or other molecular scaffolds should continue.

Název v anglickém jazyce

Influence of Experimental End Point on the Therapeutic Efficacy of Essential and Additional Antidotes in Organophosphorus Nerve Agent-Intoxicated Mice

Popis výsledku anglicky

The therapeutic efficacy of treatments for acute intoxication with highly toxic organophosphorus compounds, called nerve agents, usually involves determination of LD50 values 24 h after nerve agent challenge without and with a single administration of the treatment. Herein, the LD50 values of four nerve agents (sarin, soman, tabun and cyclosarin) for non-treated and treated in-toxication were investigated in mice for experimental end points of 6 and 24 h. The LD50 values of the nerve agents were evaluated by probit-logarithmical analysis of deaths within 6 and 24 h of i.m. challenge of the nerve agent at five different doses, using six mice per dose. The efficiency of atropine alone or atropine in combination with an oxime was practically the same at 6 and 24 h. The therapeutic efficacy of the higher dose of the antinicotinic compound MB327 was slightly higher at the 6 h end point compared to the 24 h end point for soman and tabun intoxication. A higher dose of MB327 increased the therapeutic efficacy of atropine alone for sarin, soman and tabun intoxication, and that of the standard antidotal treatment (atropine and oxime) for sarin and tabun intoxication. The therapeutic efficacy of MB327 was lower than the oxime-based anti-dotal treatment. To compare the 6 and 24 h end points, the influence of the experimental end point was not observed, with the exception of the higher dose of MB327. In addition, only a neg-ligible beneficial impact of the compound MB327 was observed. Nevertheless, antinicotinics may offer an additional avenue for countering poisoning by nerve agents that are difficult to treat, and synthetic and biological studies towards the development of such novel drugs based on the core bispyridinium structure or other molecular scaffolds should continue.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Toxics

ISSN

2305-6304

e-ISSN

2305-6304

Svazek periodika

10

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

10

Strana od-do

192

Kód UT WoS článku

000786347700001

EID výsledku v databázi Scopus

2-s2.0-85129073429