Assessment of liver slices for research on metabolic drug-drug interactions in cattle

1. Precision-cut liver slices (PCLS) from food-producing animals have not been extensively used to study xenobiotic metabolism, and thus information on this field of research is sparse. 2. The aims of the present work were to further validate the technique of production and culture of bovine PCLS an...

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Bibliographic Details
Published in:Xenobiotica 2017-11, Vol.47 (11), p.933-942
Main Authors: Viviani, Paula, Lifschitz, Adrián L., García, Jorge P., Maté, María Laura, Quiroga, Miguel A., Lanusse, Carlos E., Virkel, Guillermo L.
Format: Article
Language:English
Subjects:
Administration, Oral
Albendazole
Albendazole - analogs & derivatives
Albendazole - metabolism
Animals
Anthelmintics - metabolism
Cattle
Drug Interactions
Liver - metabolism
metabolism
Methimazole - metabolism
Microsomes, Liver - metabolism
precision-cut liver slices
Stereoisomerism
viability
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Summary:1. Precision-cut liver slices (PCLS) from food-producing animals have not been extensively used to study xenobiotic metabolism, and thus information on this field of research is sparse. 2. The aims of the present work were to further validate the technique of production and culture of bovine PCLS and to characterize the metabolic interaction between the anthelmintic albendazole (ABZ) and the flavin-monooxygenase (FMO) inhibitor methimazole (MTZ). 3. Nine steers were used as donors. PCLS were produced and incubated under two methods: a dynamic organ culture (DOC) incubator and a well-plate (WP) system. 4. Tissue viability, assessed through both structural and functional markers, was preserved throughout 12 h of incubation. ABZ was metabolized to its (+) and (-) albendazole sulfoxide stereoisomers (ABZSO) in bovine PCLS. The interaction between ABZ and MTZ resulted in a reduction (p 
ISSN:0049-8254
1366-5928
DOI:10.1080/00498254.2016.1246782