A single adulticide dose of albendazole induces cytochromes P4501A in mouflon (Ovis musimon) with dicrocoeliosis

摘要

Contact handling with wild or semi-domesticated animals requires limiting animal stress to minimum. In this respect, single administration of drug should be preferred in contact therapy of mouflon (Ovis musimon) infected by lancet fluke (Dicrocoelium dendriticum). We tested single administration of albendazole (ABZ) (30 mg/kg of body weight) in a form of oral suspension and investigated to reach anthelmintic effects and to modu- late biotransformation enzymes in liver and small intestine. Two weeks after ABZ administration coprology and necropsy findings document the adulticide effect in liver. The activities of eight biotransformation enzymes and ABZ biotransformation were tested in hepatic and intestinal subcellular fractions from control and ABZ treated animals. The highest inductive effect of ABZ was detected on cytochromes P4501A (CYP1A) activities. Increased amount of CYP1A proteins was confirmed using western blotting. In hepatic and intestinal microsomes, velocity of albendazole sulfoxide (ABZSO) formation was unaffected, but a shift in ratio of individual ABZSO enantiomers was observed. The second step of ABZ biotransformation corresponding to the formation of the pharmacologically inactive albendazole sulfone, was significantly accelerated both in liver and intestine of ABZ treated animals. The increase of ABZ deactivation could facilitate the development of anthelmintic resistance in parasites. Although single ABZ dose is therapeutically effective, its potential to induce CYP1A should be taken in account for control- ing helmithoses.