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 comparative studies on xenobiotic metabolism in swine and cattle.

3. PCLS from swine (n = 3) and cattle (n = 3) were produced using a Brendel-Vitron^TM Tissue Slicer and cultured 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) as model 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) and 7-methoxyresorufin (MROD, CYP1A2-dependent).

5. ABZ S-oxygenation resulted 6-fold (cattle) and 13.6-fold (swine) higher (p = 0.001) compared to FBZ S-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-fold higher (p = 0.0002) in swine than in cattle. Conversely, a 82% higher (p = 0.0003) rate of FBZ S-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 species differences in xenobiotic metabolism.

Keywords:

• precision-cut liver slices
• drug metabolism
• swine
• cattle

Acknowledgments

Paula Ichinose holds a doctoral fellowship granted by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data generated during and/or analysed during the current study are available from the senior author (Prof. Guillermo L. Virkel, [email protected]) upon reasonable request.

Additional information

Funding

This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) (PIP 2021-2023 - 11220200101380CO) and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) (PICT 2018-0830), both from Argentina.