title: Flubendazole metabolism and biotransformation enzymes activities in healthy sheep and sheep with haemonchosis.
abstract: The aim of this project was to study the influence of haemonchosis, a common parasitic infection of small ruminants caused by Haemonchus contortus, on the activity of biotransformation enzymes and on in vitro flubendazole (FLU) biotransformation in liver and small intestine of lambs (Ovis aries). Twelve lambs were divided into three groups: non-infected animals, animals orally infected with larvae of H. contortus ISE strain for 7 weeks and for 11 weeks. At the end of the experiment, hepatic and intestinal subcellular fractions were prepared and used for assays of biotransformation enzymes activities and FLU metabolism testing. The activities of hepatic cytochromes P450, flavine monooxygenases and carbonyl-reducing enzymes were decreased in infected animals. UDP-glucuronosyl transferase activity was significantly lower (by 35%) in 11 weeks infected animals than that in control animals. When in vitro metabolism of FLU was compared in control and infected animals, significantly lower velocity of FLU reduction was found in infected animals. Slower FLU reduction may be beneficial for the haemonchosis treatment using FLU, because FLU will remain longer in the organism and could cause longer contact of parasites with FLU.
authors.affiliation: Faculty of Pharmacy, Charles University, Heyrovského, Hradec Králové, Czech Republic.
authors.forename: H
authors.initials: H
authors.lastname: Bártíková
authors.forename: V
authors.initials: V
authors.lastname: Krízová
authors.forename: J
authors.initials: J
authors.lastname: Lamka
authors.forename: V
authors.initials: V
authors.lastname: Kubícek
authors.forename: L
authors.initials: L
authors.lastname: Skálová
authors.forename: B
authors.initials: B
authors.lastname: Szotáková
mesh_terms: D000818:Animals; D001711:Biotransformation; D006188:Haemonchiasis / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D006189:Haemonchus / Q000187:drug effects; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008463:Mebendazole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D012756:Sheep; D012757:Sheep Diseases / Q000378:metabolism*
chemical_list: D008463:Mebendazole; C018945:flubendazole