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Biotransformation of anthelmintics and the activity of drug-metabolizing enzymes in the tapeworm Moniezia expansa

Published online by Cambridge University Press:  06 November 2014

LUKÁŠ PRCHAL ,
HANA BÁRTÍKOVÁ ,
ANETA BEČANOVÁ ,
ROBERT JIRÁSKO ,
IVAN VOKŘÁL ,
LUCIE STUCHLÍKOVÁ ,
LENKA SKÁLOVÁ ,
VLADIMÍR KUBÍČEK ,
JIŘÍ LAMKA  and
FRANTIŠEK TREJTNAR
...Show all authors
LUKÁŠ PRCHAL
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
HANA BÁRTÍKOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
ANETA BEČANOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
ROBERT JIRÁSKO
Affiliation:
Faculty of Chemical Technology, University of Pardubice, Studentská 573, CZ-53210 Pardubice, Czech Republic
IVAN VOKŘÁL
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
LUCIE STUCHLÍKOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
LENKA SKÁLOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
VLADIMÍR KUBÍČEK
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
JIŘÍ LAMKA
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
FRANTIŠEK TREJTNAR
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
BARBORA SZOTÁKOVÁ*
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
*
*Corresponding author. Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. E-mail: Barbora.Szotakova@faf.cuni.cz
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Summary

The sheep tapeworm Moniezia expansa is very common parasite, which affects ruminants such as sheep, goats as well as other species. The benzimidazole anthelmintics albendazole (ABZ), flubendazole (FLU) and mebendazole (MBZ) are often used to treat the infection. The drug-metabolizing enzymes of helminths may alter the potency of anthelmintic treatment. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (ABZ, MBZ and FLU) in M. expansa. Activities of biotransformation enzymes were determined in subcellular fractions. Metabolites of the anthelmintics were detected and identified using high performance liquid chromatography/ultra-violet/VIS/fluorescence or ultra-high performance liquid chromatography/mass spectrometry. Reduction of MBZ, FLU and oxidation of ABZ were proved as well as activities of various metabolizing enzymes. Despite the fact that the conjugation enzymes glutathione S-transferase, UDP-glucuronosyl transferase and UDP-glucosyl transferase were active in vitro, no conjugated metabolites of anthelmintics were identified either ex vivo or in vitro. The obtained results indicate that sheep tapeworm is able to deactivate the administered anthelmintics, and thus protects itself against their action.

Keywords

Monieziadrug metabolismanthelminticbenzimidazolealbendazole
Type
Research Article
Information
Parasitology , Volume 142 , Issue 5 , April 2015 , pp. 648 - 659
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Copyright
Copyright © Cambridge University Press 2014 

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