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Parasitology

Table of Contents - September 2012 - Volume 139, Issue 10  

Research Article

The metabolism of flubendazole and the activities of selected biotransformation enzymes in Haemonchus contortus strains susceptible and resistant to anthelmintics

IVAN VOKŘÁLa1, HANA BÁRTÍKOVÁa1, LUKÁŠ PRCHALa1, LUCIE STUCHLÍKOVÁa1, LENKA SKÁLOVÁa1, BARBORA SZOTÁKOVÁa1, JIŘÍ LAMKAa1, MARIÁN VÁRADYa2 and VLADIMÍR KUBÍČEKa1 c1

a1 Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic

a2 Institute of Parasitology, Slovak Academy of Sciences, Košice, Slovakia

SUMMARY

Haemonchus contortus is one of the most pathogenic parasites of small ruminants (e.g. sheep and goat). The treatment of haemonchosis is complicated because of recurrent resistance of H. contortus to common anthelmintics. The aim of this study was to compare the metabolism of the anthelmintic drug flubendazole (FLU) and the activities of selected biotransformation enzymes towards model xenobiotics in 4 different strains of H. contortus: the ISE strain (susceptible to common anthelmintics), ISE-S (resistant to ivermectin), the BR strain (resistant to benzimidazole anthelmintics) and the WR strain (resistant to all common anthelmintics). H. contortus adults were collected from the abomasums from experimentally infected lambs. The in vitro as well as ex vivo experiments were performed and analysed using HPLC with spectrofluorimetric and mass-spectrometric detection. In all H. contortus strains, 4 different FLU metabolites were detected: FLU with a reduced carbonyl group (FLU-R), glucose conjugate of FLU-R and 2 glucose conjugates of FLU. In the resistant strains, the ex vivo formation of all FLU metabolites was significantly higher than in the susceptible ISE strain. The multi-resistant WR strain formed approximately 5 times more conjugates of FLU than the susceptible ISE strain. The in vitro data also showed significant differences in FLU metabolism, in the activities of UDP-glucosyltransferase and several carbonyl-reducing enzymes between the susceptible and resistant H. contortus strains. The altered activities of certain detoxifying enzymes might protect the parasites against the toxic effect of the drugs as well as contribute to drug-resistance in these parasites.

(Received November 15 2011)

(Revised January 23 2012)

(Revised February 20 2012)

(Accepted March 09 2012)

(Online publication May 01 2012)

Key words

Correspondence:

c1 Corresponding author: Faculty of Pharmacy, Charles University, Heyrovského 1203, Hradec Králové, CZ-500 05 Czech Republic. Tel: 00420 495 067 410. E-mail: kubicek@faf.cuni.cz

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