Ivermectin-induced changes in the expression of cytochromes P450 and efflux transporters in Haemonchus contortus female and male adults
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
31442889
DOI
10.1016/j.vetpar.2019.07.006
PII: S0304-4017(19)30169-4
Knihovny.cz E-resources
- Keywords
- Anthelmintics, Drug resistance, Macrocyclic lactones, Nematode, Sex-differences,
- MeSH
- Haemonchus drug effects genetics MeSH
- Ivermectin pharmacology MeSH
- Drug Resistance genetics MeSH
- ATP Binding Cassette Transporter, Subfamily B genetics MeSH
- Gene Expression Regulation drug effects MeSH
- Cytochrome P-450 Enzyme System genetics MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Ivermectin MeSH
- ATP Binding Cassette Transporter, Subfamily B MeSH
- Cytochrome P-450 Enzyme System MeSH
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 IVM (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 sub-lethal 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.
References provided by Crossref.org
Biotransformation of anthelmintics in nematodes in relation to drug resistance
UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus
