Effects of fenbendazole and triclabendazole on the expression of cytochrome P450 1A and flavin-monooxygenase isozymes in bovine precision-cut liver slices

• Published in: The veterinary journal (1997) 2019-03, Vol.245, p.61-69
• Main Authors: Maté, L., Giantin, M., Viviani, P., Ballent, M., Tolosi, R., Lifschitz, A., Lanusse, C., Dacasto, M., Virkel, G.
• Format: Article
• Language: English
• Subjects: Benzimidazole anthelmintics; Cattle liver slices; Cytochrome P450 isoenzymes; Flavin-monooxygenases; β-naphtoflavone
• ISSN: 1090-0233; 1532-2971
• DOI: 10.1016/j.tvjl.2019.01.001

•Bovine precision-cut liver slices (PCLSs) expressed cytochrome P450 1A (CYP1A) and flavin monooxygenase (FMO) mRNAs.•In bovine PCLSs, the CYP inducer β-naphtoflavone increased CYP1A1, CYP1A2, FMO1 and FMO3 mRNAs.•Fenbendazole (FBZ) slightly up-regulated CYP1As and FMOs, but this was not the case for triclabendazole (TCBZ), or FBZ+TCBZ.•The observed transcriptional effects were not mirrored by changes in the catalytic activities of the isozymes under study.•Bovine PCLSs may represent an alternative in vitro tool for bovine drug metabolism studies. Combinations of the anthelmintics fenbendazole (FBZ) and triclabendazole (TCBZ) have shown enhanced efficacy against the liver fluke Fasciola hepatica. This study aimed to measuring the constitutive expression of CYP1A1, CYP1A2, FMO1 and FMO3, thought to be involved in the metabolism of those compounds, by using an absolute quantitative real time (RT)-PCR approach in bovine precision-cut liver slices (PCLS). It also aimed to characterize the effects of FBZ and TCBZ (alone and in combination) on the expression and activity of the aforementioned isozymes. Both FMO1 and FMO3 were equally represented in control PCLS, whereas CYP1A2 was expressed more than CYP1A1 (P