Biotransformation of albendazole and activities of selected detoxification enzymes in Haemonchus contortus strains susceptible and resistant to anthelmintics
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23587403
DOI
10.1016/j.vetpar.2013.03.018
PII: S0304-4017(13)00163-5
Knihovny.cz E-resources
- Keywords
- ABZ, ABZ-SO, ABZ-SO(2), Drug resistance, Nematodes, Strain-differences, UDP-glucosyltransferase, albendazole, albendazole sulfone, albendazole sulfoxide,
- MeSH
- Enzyme Activation drug effects MeSH
- Albendazole chemistry metabolism pharmacology MeSH
- Anthelmintics metabolism pharmacology MeSH
- Haemonchus drug effects enzymology metabolism MeSH
- Catalase metabolism MeSH
- Drug Resistance * MeSH
- Molecular Structure MeSH
- Sheep Diseases parasitology MeSH
- Sheep MeSH
- Peroxidase metabolism MeSH
- Superoxide Dismutase metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Albendazole MeSH
- Anthelmintics MeSH
- Catalase MeSH
- Peroxidase MeSH
- Superoxide Dismutase MeSH
The increased activity of drug-metabolizing enzymes can protect helminths against the toxic effect of anthelmintics. The aim of this study was to compare the metabolism of the anthelmintic drug albendazole (ABZ) and the activities of selected biotransformation and antioxidant enzymes in three different strains of Haemonchus contortus: the ISE strain (susceptible to common anthelmintics), the BR strain (resistant to benzimidazole anthelmintics) and the WR strain (multi-resistant). H. contortus adults were collected from the abomasum of experimentally infected lambs. In vitro (subcellular fractions of H. contortus homogenate) as well as ex vivo (living nematodes cultivated in flasks with medium) experiments were performed. HPLC with spectrofluorimetric and mass-spectrometric detection was used in the analysis of ABZ metabolites. The in vitro activities of oxidation/antioxidation and conjugation enzymes toward model substrates were also assayed. The in vitro data showed significant differences between the susceptible (ISE) and resistant (BR, WR) strains regarding the activities of peroxidases, catalase and UDP-glucosyltransferases. S-oxidation of ABZ was significantly lower in BR than in the ISE strain. Ex vivo, four ABZ metabolites were identified: ABZ sulphoxide and three ABZ glucosides. In the resistant strains BR and WR, the ex vivo formation of all ABZ glucosides was significantly higher than in the susceptible ISE strain. The altered activities of certain detoxifying enzymes might partly protect the parasites against the toxic effect of the drugs as well as contribute to drug-resistance in these parasites.
References provided by Crossref.org
UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus
The Identification of Metabolites and Effects of Albendazole in Alfalfa (Medicago sativa)
