Effect of P-glycoprotein on the availability of oxime reactivators in the brain

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F20%3A00556186" target="_blank" >RIV/60162694:G44__/20:00556186 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/20:10418532

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0300483X20301803?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0300483X20301803?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tox.2020.152541" target="_blank" >10.1016/j.tox.2020.152541</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effect of P-glycoprotein on the availability of oxime reactivators in the brain

Popis výsledku v původním jazyce

The ability to overcome cellular barriers in the body is crucial for efficient delivery of drugs to the target where intervention is needed. For drugs acting in the brain it is essential to overcome the blood-brain barrier (BBB). Such drugs include antidotes for the treatment of organophosphate poisoning, a current warfare and terroristic threat. Being lipophilic compounds, organophosphates readily penetrate the brain and block the enzyme acetylcholinesterase (AChE). They cause severe symptoms which may have fatal consequences. A major drawback of currently available oxime reactivators is their inability to reactivate AChE in the central nervous system (CNS) as they are unable to cross the blood-brain barrier. An important obstacle preventing many drugs from reaching their therapeutic target in the brain is the efflux transporter P-glycoprotein (P-gp), whose function is to prevent the penetration of potentially harmful substances. The aim of this study was to evaluate the effect of P-gp on the permeation of oximes into the brain. The study of this interaction was carried out on the CACO-2 cell line, stably expressing P-gp. As it turned out, P-gp has no essential influence on the central availability of clinically used oxime reactivators within this study.

Název v anglickém jazyce

Effect of P-glycoprotein on the availability of oxime reactivators in the brain

Popis výsledku anglicky

The ability to overcome cellular barriers in the body is crucial for efficient delivery of drugs to the target where intervention is needed. For drugs acting in the brain it is essential to overcome the blood-brain barrier (BBB). Such drugs include antidotes for the treatment of organophosphate poisoning, a current warfare and terroristic threat. Being lipophilic compounds, organophosphates readily penetrate the brain and block the enzyme acetylcholinesterase (AChE). They cause severe symptoms which may have fatal consequences. A major drawback of currently available oxime reactivators is their inability to reactivate AChE in the central nervous system (CNS) as they are unable to cross the blood-brain barrier. An important obstacle preventing many drugs from reaching their therapeutic target in the brain is the efflux transporter P-glycoprotein (P-gp), whose function is to prevent the penetration of potentially harmful substances. The aim of this study was to evaluate the effect of P-gp on the permeation of oximes into the brain. The study of this interaction was carried out on the CACO-2 cell line, stably expressing P-gp. As it turned out, P-gp has no essential influence on the central availability of clinically used oxime reactivators within this study.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/NV17-32801A" target="_blank" >NV17-32801A: Centrálně účinná antidota pro léčbu otrav organofosfáty</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Toxicology

ISSN

0300-483X

e-ISSN

1879-3185

Svazek periodika

443

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

4

Strana od-do

152541

Kód UT WoS článku

000575194600010

EID výsledku v databázi Scopus

2-s2.0-85089890168