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Parasitology

Table of Contents - May 2012 - Volume 139, Issue 06  

Research Article

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

HANA BÁRTÍKOVÁa1, IVAN VOKŘÁLa1, LENKA SKÁLOVÁa1, VLADIMÍR KUBÍČEKa1, JANA FIRBASOVÁa1, DAVID BRIESTENSKÝa1, JIŘÍ LAMKAa1 and BARBORA SZOTÁKOVÁa1 c1

a1 Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic

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.

(Received July 01 2011)

(Revised September 15 2011)

(Revised November 07 2011)

(Accepted November 13 2011)

(Online publication February 06 2012)

Key words

Correspondence:

c1 Corresponding author: Tel: +420 495 067 324. Fax: +420 495 067 168. E-mail: Barbora.Szotakova@faf.cuni.cz

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