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Biotransformation of anthelmintics and the activity of drug-metabolizing enzymes in the tapeworm Moniezia expansa
Authors: Prchal Lukas | Bartikova Hana | Becanova Aneta | Jirásko Robert | Vokral Ivan | Stuchlikova Lucie | Skalova Lenka | Kubicek Vladimir | Lamka Jiri | Trejtnar Frantisek | Szotakova Barbora
Year: 2015
Type of publication: článek v odborném periodiku
Name of source: Parasitology
Publisher name: Cambridge University Press
Place: New York
Page from-to: 648-659
Titles:
Language Name Abstract Keywords
cze Studium biotransformace anthelmintik a aktivity enzymů metabolizujicích tyto lečiva v tasemnici Moniezia expansa Ovčí tasemnice Moniezia expansa je běžný parazit, který napadá přežvýkavce. Proti těmto parazitům se často využívají benzimidazolová lečiva albendazol (ABZ), flubendazol (FLU) a mebendazol (MBZ). Enzymy helmitů metabolizující anthelmintika mohou léčbu výrazně ovlinit. Cílem této práce bylo stanovit aktivitu těchto enzymů a určit metabolismus vybraných léčiv (ABZ, FLU, MBZ) v Moniezia expansa s využitím UHPLC/MS/MS.
eng Biotransformation of anthelmintics and the activity of drug-metabolizing enzymes in the tapeworm Moniezia expansa 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. Moniezia; drug metabolism; anthelmintic; benzimidazole; albendazole

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