Ivermectin-induced changes in the expression of cytochromes P450 and efflux transporters in Haemonchus contortus female and male adults

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F19%3A10399901" target="_blank" >RIV/00216208:11160/19:10399901 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Pt.W5wBWP2" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Pt.W5wBWP2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.vetpar.2019.07.006" target="_blank" >10.1016/j.vetpar.2019.07.006</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ivermectin-induced changes in the expression of cytochromes P450 and efflux transporters in Haemonchus contortus female and male adults

Popis výsledku v původním jazyce

Haemonchus contortus, one of the most pathogenic of all small ruminant parasites, have developed resistance to all used anthelmintics. Detoxification enzymes, e.g. cytochromes P450 (CYPs) and efflux transporters P-glycoproteins (P-gps), which represent the main defense system against harmful xenobiotics, have been suggested to contribute to drug resistance development. The present study was designed to compare the constitutive expression of individual CYPs and P-gps in females and males of H. contortus adults and to follow up on the changes in expression of these genes in nematodes exposed to sub-lethal concentrations of ivermectin (IVM), which might occur during inaccurate treatment. The adults of inbred susceptible-Edinburgh strain (ISE, MHco3) of H. contortus were used for this purpose. The nematodes were incubated ex vivo with or without 1VM (1, 10 and 100 nM) in culture medium for 4, 12 and 24 h. After incubation, total RNA was isolated and expression levels of individual CYPs and P-gps were analyzed using qPCR. Our results showed a great variability in the constitutive expression of individual CYPs and P-gps in H. contortus adults. The constitutive expression as well as the inducibility of CYPs and P-gps significantly differed in males and females. Contact of adult nematodes with sublethal IVM concentrations led to only minor changes in expression of CYPs, while expression of several P-gps, particularly pgp-9.2 in males and pgp-10, pgp-11 in females was increased significantly in IVM-exposed nematodes. In conclusion, inaccurate treatment of sheep with IVM might contribute to drug resistance development via increased expression of efflux transporters in H. contortus adults.

Název v anglickém jazyce

Ivermectin-induced changes in the expression of cytochromes P450 and efflux transporters in Haemonchus contortus female and male adults

Popis výsledku anglicky

Haemonchus contortus, one of the most pathogenic of all small ruminant parasites, have developed resistance to all used anthelmintics. Detoxification enzymes, e.g. cytochromes P450 (CYPs) and efflux transporters P-glycoproteins (P-gps), which represent the main defense system against harmful xenobiotics, have been suggested to contribute to drug resistance development. The present study was designed to compare the constitutive expression of individual CYPs and P-gps in females and males of H. contortus adults and to follow up on the changes in expression of these genes in nematodes exposed to sub-lethal concentrations of ivermectin (IVM), which might occur during inaccurate treatment. The adults of inbred susceptible-Edinburgh strain (ISE, MHco3) of H. contortus were used for this purpose. The nematodes were incubated ex vivo with or without 1VM (1, 10 and 100 nM) in culture medium for 4, 12 and 24 h. After incubation, total RNA was isolated and expression levels of individual CYPs and P-gps were analyzed using qPCR. Our results showed a great variability in the constitutive expression of individual CYPs and P-gps in H. contortus adults. The constitutive expression as well as the inducibility of CYPs and P-gps significantly differed in males and females. Contact of adult nematodes with sublethal IVM concentrations led to only minor changes in expression of CYPs, while expression of several P-gps, particularly pgp-9.2 in males and pgp-10, pgp-11 in females was increased significantly in IVM-exposed nematodes. In conclusion, inaccurate treatment of sheep with IVM might contribute to drug resistance development via increased expression of efflux transporters in H. contortus adults.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Veterinary Parasitology

ISSN

0304-4017

e-ISSN

—

Svazek periodika

273

Číslo periodika v rámci svazku

September

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

24-31

Kód UT WoS článku

000487570500005

EID výsledku v databázi Scopus

2-s2.0-85071977218