title: Assessment of liver slices for research on metabolic drug-drug interactions in cattle.
abstract: 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 < 0.001) in the rates of appearance of (+) ABZSO. Conversely, in presence of MTZ, the rates of appearance of (-) ABZSO increased under both systems (p < 0.05). 5. Both culture systems were suitable for assessing the interaction between ABZ and MTZ. 6. Overall, the results presented herein show that PCLS are a useful and reliable tool for short-term studies on metabolic drug-drug interactions in the bovine species.
authors: a Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN, CONICET-CIC-UNCPBA) , Tandil , Argentina.
authors: Paula
authors: P
authors: Viviani
authors: a Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN, CONICET-CIC-UNCPBA) , Tandil , Argentina.
authors: Adrián L
authors: AL
authors: Lifschitz
authors: a Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN, CONICET-CIC-UNCPBA) , Tandil , Argentina.
authors: Jorge P
authors: JP
authors: García
authors: a Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN, CONICET-CIC-UNCPBA) , Tandil , Argentina.
authors: María Laura
authors: ML
authors: Maté
authors: a Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN, CONICET-CIC-UNCPBA) , Tandil , Argentina.
authors: Miguel A
authors: MA
authors: Quiroga
authors: a Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN, CONICET-CIC-UNCPBA) , Tandil , Argentina.
authors: Carlos E
authors: CE
authors: Lanusse
authors: a Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN, CONICET-CIC-UNCPBA) , Tandil , Argentina.
authors: Guillermo L
authors: GL
authors: Virkel
mesh_terms: D000284:Administration, Oral; D015766:Albendazole / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000378:metabolism; D002417:Cattle; D004347:Drug Interactions; D008099:Liver / Q000378:metabolism*; D008713:Methimazole / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000871:Anthelmintics; D008713:Methimazole; D015766:Albendazole; C027186:albendazole sulfoxide
keywords: Albendazole; cattle; metabolism; precision-cut liver slices; viability