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The activity of drug-metabolizing enzymes and the biotransformation of selected anthelmintics in the model tapeworm Hymenolepis diminuta

Published online by Cambridge University Press:  06 February 2012

HANA BÁRTÍKOVÁ ,
IVAN VOKŘÁL ,
LENKA SKÁLOVÁ ,
VLADIMÍR KUBÍČEK ,
JANA FIRBASOVÁ ,
DAVID BRIESTENSKÝ ,
JIŘÍ LAMKA  and
BARBORA SZOTÁKOVÁ
HANA BÁRTÍKOVÁ
Affiliation:
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
IVAN VOKŘÁL
Affiliation:
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
LENKA SKÁLOVÁ
Affiliation:
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
VLADIMÍR KUBÍČEK
Affiliation:
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
JANA FIRBASOVÁ
Affiliation:
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
DAVID BRIESTENSKÝ
Affiliation:
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
JIŘÍ LAMKA
Affiliation:
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
BARBORA SZOTÁKOVÁ*
Affiliation:
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
*
*Corresponding author: Tel: +420 495 067 324. Fax: +420 495 067 168. E-mail: Barbora.Szotakova@faf.cuni.cz
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Summary

The drug-metabolizing enzymes of some helminths can deactivate anthelmintics and therefore partially protect helminths against these drugs' toxic effect. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (albendazole, flubendazole, mebendazole) in the rat tapeworm Hymenolepis diminuta, a species often used as a model tapeworm. In vitro and ex vivo experiments were performed. Metabolites of the anthelmintics were detected and identified by HPLC with spectrofluorometric or mass–spectrometric detection. The enzymes of H. diminuta are able to reduce the carbonyl group of flubendazole, mebendazole and several other xenobiotics. Although the activity of a number of oxidation enzymes was determined, no oxidative metabolites of albendazole were detected. Regarding conjugation enzymes, a high activity of glutathione S-transferase was observed. A methyl derivative of reduced flubendazole was the only conjugation metabolite identified in ex vivo incubations of H. diminuta with anthelmintics. The results revealed that H. diminuta metabolized flubendazole and mebendazole, but not albendazole. The biotransformation pathways found in H. diminuta differ from those described in Moniezia expanza and suggest the interspecies differences in drug metabolism not only among classes of helminths, but even among tapeworms.

Keywords

biotransformation enzymesdrug metabolismalbendazoleflubendazolemebendazoleliquid chromatography/mass spectrometry

Information

Type
Research Article
Information
Parasitology , Volume 139 , Issue 6 , May 2012 , pp. 809 - 818
Copyright
Copyright © Cambridge University Press 2012

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