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.
Faculty of Pharmacy,Charles University,Heyrovského 1203,CZ-50005 Hradec Králové,Czech Republic.
Lukáš
L
Prchal
Faculty of Pharmacy,Charles University,Heyrovského 1203,CZ-50005 Hradec Králové,Czech Republic.
Hana
H
Bártíková
Faculty of Pharmacy,Charles University,Heyrovského 1203,CZ-50005 Hradec Králové,Czech Republic.
Aneta
A
Bečanová
Faculty of Chemical Technology,University of Pardubice,Studentská 573,CZ-53210 Pardubice,Czech Republic.
Robert
R
Jirásko
Faculty of Pharmacy,Charles University,Heyrovského 1203,CZ-50005 Hradec Králové,Czech Republic.
Ivan
I
Vokřál
Faculty of Pharmacy,Charles University,Heyrovského 1203,CZ-50005 Hradec Králové,Czech Republic.
Lucie
L
Stuchlíková
Faculty of Pharmacy,Charles University,Heyrovského 1203,CZ-50005 Hradec Králové,Czech Republic.
Lenka
L
Skálová
Faculty of Pharmacy,Charles University,Heyrovského 1203,CZ-50005 Hradec Králové,Czech Republic.
Vladimír
V
Kubíček
Faculty of Pharmacy,Charles University,Heyrovského 1203,CZ-50005 Hradec Králové,Czech Republic.
Jiří
J
Lamka
Faculty of Pharmacy,Charles University,Heyrovského 1203,CZ-50005 Hradec Králové,Czech Republic.
František
F
Trejtnar
Faculty of Pharmacy,Charles University,Heyrovského 1203,CZ-50005 Hradec Králové,Czech Republic.
Barbora
B
Szotáková
D015766:Albendazole / Q000493:pharmacokinetics* / Q000494:pharmacology; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics* / Q000494:pharmacology; D001711:Biotransformation; D002374:Catalase / Q000378:metabolism; D002589:Cestoda / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007421:Intestine, Small / Q000469:parasitology; D007527:Isoenzymes / Q000378:metabolism; D008463:Mebendazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008989:Monieziasis / Q000469:parasitology; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D012756:Sheep; D012757:Sheep Diseases / Q000469:parasitology; D013482:Superoxide Dismutase / Q000378:metabolism; D000099148:UGT1A1 Enzyme
D015766:Albendazole; D000429:Alcohol Oxidoreductases; D000871:Anthelmintics; D002374:Catalase; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D007527:Isoenzymes; D008463:Mebendazole; D006899:Mixed Function Oxygenases; D009097:Multienzyme Complexes; D009247:NADH, NADPH Oxidoreductases; D009195:Peroxidase; D013482:Superoxide Dismutase; D000099148:UGT1A1 Enzyme; C466433:thioredoxin glutathione reductase; C018945:flubendazole
albendazole