Exploring precision-cut liver slices for comparative xenobiotic metabolism profiling in swine and cattle

Abstract

1. In vitro systems are useful tools for unravelling species differences in xenobiotic metabolism.2. The current work aimed to validate the technique of precision-cut liver slices (PCLS) for comparativestudies on xenobiotic metabolism in swine and cattle.3. PCLS from swine (n = 3) and cattle (n = 3) were produced using a Brendel-VitronTM Tissue Slicer andcultured for 6 h. Tissue viability was preserved throughout the whole culture period.4. Metabolic viability was evaluated using the anthelmintics albendazole (ABZ) and fenbendazole (FBZ) asmodel drugs, as well as other substrates of hepatic monooxygenases: benzydamine (BZ) N-oxygenase(FMO-dependent), and the O-dealkylations of 7-ethoxyresorufin (EROD, CYP1A1-dependent) and7-methoxyresorufin (MROD, CYP1A2-dependent).5. ABZ S-oxygenation resulted 6-fold (cattle) and 13.6-fold (swine) higher (p = 0.001) compared to FBZS-oxygenation.6. Similar BZ N-oxygenation and EROD activities were observed in PCLS cultures from both species.MROD was 2.5-fold higher (p = 0.033) in swine than in cattle. Similarly, ABZ S-oxygenation was 1.7-foldhigher (p = 0.0002) in swine than in cattle. Conversely, a 82% higher (p = 0.0003) rate of FBZS-oxygenation was evidenced in PCLS cultures from cattle compared to those from swine.7. Overall, this work shows that PCLS cultures are useful to obtain relevant information on speciesdifferences in xenobiotic metabolism.