Activities of biotransformation enzymes and flubendazole metabolism in lambs (Ovis aries): effect of gender and flubendazole therapy.
The effect of flubendazole (FLU) therapy on in vitro FLU biotransformation and the activities of selected biotransformation enzymes were investigated in male and female lambs. Four experimental groups were used: control (untreated) ewes and rams and FLU-treated ewes and rams (orally, 15 mg/kg per day, for three consecutive days). Subcellular fractions were prepared from liver and intestinal mucosa 24 h after the final dosage was administered. Activities of cytochromes P450 (CYP), flavine monooxygenases (FMO), carbonyl reducing enzymes, UDP-glucuronosyl transferase (UGT) and glutathione S-transferase were tested. Significant gender differences were observed for FMO-mediated activity (2-fold higher in ram lambs) and UGT activity (up to 30% higher in ewe lambs), but no gender differences were observed in FLU metabolism. FLU-treatment of lambs moderately changed the activities of some CYPs, FMO, and UGT in liver microsomes. In vitro FLU reduction was not altered in the liver, but was slightly higher in the small intestine of FLU pre-treated lambs. This correlated with the higher carbonyl reductase activities measured in the gut mucosa of these animals.
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. Barbora.Szotakova@faf.cuni.cz
Hana
H
Bártíková
Veronika
V
Krízová
Martina
M
Stepnicková
Jirí
J
Lamka
Vladimír
V
Kubícek
Lenka
L
Skálová
Barbora
B
Szotáková
D000818:Animals; D000969:Antinematodal Agents / Q000378:metabolism*; D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism; D005260:Female; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008463:Mebendazole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D012727:Sex Characteristics; D012756:Sheep
D000969:Antinematodal Agents; D008463:Mebendazole; C018945:flubendazole