Effect of repeated administration of flubendazole on ovine biotransformation enzymes

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Title, Name, Surname of candidate: Martina Štěpničková Title, Name, Surname of tutor: Doc. Ing. Barbora Szotáková, Ph.D. Title of a diploma work: Modulation of biotransformation enzymes by repeated administration of flubendazole in domestic sheep. Flubendazole is benzimidazole anthelmintic widely used in veterinary medicine for treatment and prevention of helminthosis in domestic and wild animals. Currently the effectiveness of available anthelmintics is being diminished by the worms newly formed resistance mechanisms. This work was designed to test the influence of flubendazole on cytochrome P450 isoforms, flavine monooxygenases, some carbonyl reducing enzymes, glutathion S-transferase and UDP-glucuronosyl transferase in domestic sheep. Activities of these enzymes were observed in subcellular fractions which were prepared from the liver and small intestine of the following groups of tested subjects: control sheeps, flubendazole treated sheeps and Haemonchus contortus infected sheeps that were subsequently treated by flubendozole. Flubendazole was administered to each sheep three times in a dose of 15mg/kg. The results indicated that flubendazole does not influence the activity of CYP 2B, CYP 3A,..