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The Inability of Tapeworm Hymenolepis Diminuta and Fluke Dicrocoelium Dendriticum to Metabolize Praziquantel
Authors: Vokřál Ivan | Jirásko Robert | Jedličková Veronika | Bártíková Hana | Skálová Lenka | Lamka Jiří | Holčapek Michal | Szotáková Barbora
Year: 2012
Type of publication: článek v odborném periodiku
Name of source: Veterinary Parasitology
Publisher name: Elsevier Science BV
Place: Amsterdam
Page from-to: 168-174
Titles:
Language Name Abstract Keywords
cze Neschopnost tasemnice Hymenolepis diminuta a motolice Dicrocoelium dendriticum metabolizovat praziquantel V této práci jsou popsány postupy analytické charakterizace pro získání informací o potenciálních metabolitech 1. a 2. fáze léčiva praziquantel ve vzorcích tasemnic a motolic. Dále jsou zde popsány metabolity praziquantelu v in vivo a in vitro vzorcích potkana. K těmto účelům bylo využito spojení UHPLC/MS/MS. Biotransformace; Dicrocoelium dendriticum; Hymenolepis diminuta; Praziquantel
eng The Inability of Tapeworm Hymenolepis Diminuta and Fluke Dicrocoelium Dendriticum to Metabolize Praziquantel Biotransformation enzymes can, to a certain extent, protect parasitic worms against the toxic effects of anthelmintics and can contribute to drug-resistance development. The objective of our work was (1) to find and identify phase I and II metabolites of the anthelmintic praziquantel (PZQ) formed by the lancet fluke (Dicrocoelium dendriticum) and the rat tapeworm (Hymenolepis diminuta) and (2) to compare PZQ metabolites in helminths with PZQ biotransformation in rat as host species. Ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) was used for this purpose. During in vitro incubations, mitochondria-like and microsomes-like fractions (prepared from homogenates of adult worms or from rat liver homogenate) were incubated with 10 and 100 mu M PZQ. Liquid/liquid extraction was used for samples during in vitro experiments. In the ex vivo study, living D. dendriticum and H. diminuta adults were incubated in RPMI-1640 medium in the presence of 50 nM or 100 nM PZQ for 24 h. After incubation, the worms were removed from the medium and homogenized. Homogenates of worms, medium from the incubation of worms or rat hepatocytes and rat urine (collected during 24 h after oral PZQ administration) were separately extracted using solid-phase extraction. The results showed that both D. dendriticum and H. diminuta enzymatic systems are not able to metabolize PZQ. On the other hand, thirty one different phase I and four phase II PZQ metabolites were detected in rat samples using UHPLC/MS/MS analyses. These results show that our experimental helminths, as the members of tapeworm and fluke groups of parasites, are not able to deactivate PZQ, and that the biotransformation enzymes of the studied helminths do not contribute to PZQ-resistance. Praziquantel; Hymenolepis diminuta; Dicrocoelium dendriticum; Biotransformation

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