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

Abstract

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 modulate 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 controling helmithoses.

Pharmacokinetics of flubendazole and its metabolites in lambs and adult sheep (Ovis aries)

“…In summary an effective therapy of systemic parasitoses, for example in lung or liver, generally requires either a single administration of a high dose of a drug (Ramisz et al. , 1979; Lamka et al. , 2007) or the use of lower doses but administered in long‐term schemes (Ramisz et al.…”

“…In the present study, the administration of a single and higher dose of FLU was chosen because this mode of administration generally proved highly effective and is simultaneously well tolerated by treated animals (http://www.emea.europa.eu/htms/vet/mrls; Dayan, 2003). The decision to use the aforementioned approach was also supported by a good therapeutic experience with identically administered albendazole (Lamka et al. , 2007), where optimal therapeutic effectivity was reached against parasites located in the bile ducts of liver (dicrocoeliosis), which are assumed as therapeutically very resistant parasites.…”

“…Benzimidazoles are used for the control of parasitoses in sheep in different dosage schemes: a single dose administration (Ramisz et al, 1979;Heimonas et al, 1980;Bliss & Greiner, 1985) and long-term (continual) administration of a drug over several months (Dorchies et al, 1988) represent boundary limits from the point of duration of drug administration. In summary an effective therapy of systemic parasitoses, for example in lung or liver, generally requires either a single administration of a high dose of a drug (Ramisz et al, 1979;Lamka et al, 2007) or the use of lower doses but administered in long-term schemes (Ramisz et al, 1979;Lamka et al, 1996;Kassai, 1999). In the present study, the administration of a single and higher dose of FLU was chosen because this mode of administration generally proved highly effective and is simultaneously well tolerated by treated animals (http://www.emea.europa.eu/htms/vet/mrls; Dayan, 2003).…”

Dicrocoeliosis of Old Mouflon Ewes - Effect on Biotransformation Enzymes and Metabolism of Anthelmintics In Vitro

“…The strategic treatment of all animals exposed to infection by free grazing is the most common option for dicrocoeliosis control [6]. Several benzimidazoles, probenzimidazoles, praziquantel, closantel, oxyclosanid and diamphenetid have been verified for treatment of dicrocoeliosis [7].…”

Strategic control of Dicrocoelium dendriticum (Digenea) egg excretion by naturally infected sheep

“…Moreover, the authors pointed out that as mouflon and domestic sheep are phylogenetically two forms of identical species, the experimental data found in one can also be used for the other. Lamka et al (2007) treated adult female mouflons infected with D. dendriticum with a single dose of ABZ (30 mg/kg of body weight; oral route). The ABZ administration was very effective because the faecal EPG values decreased rapidly and was very low by the 7 th day after treatment.…”