Induction of cytochrome P450 enzymes in primary equine hepatocytes culture

Stefanski, A (2013). Induction of cytochrome P450 enzymes in primary equine hepatocytes culture. (Dissertation, Department of Clinical Research and Veterinary Public Health, Veterinär-Pharmakologie und -Toxikologie, Vetsuisse Fakultät Bern)

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Cytochrome P450 enzymes (CYPs) are responsible for the oxidative metabolism of a wide variety of substances including the majority of drugs. An induction or inhibition of their metabolic activity can therefore change the elimination of drugs from the body dramatically. Due to significant differences between species, CYPs of each domestic species should be characterized individually. To date, no studies on CYP induction in the horse have been published. In this study, we investigated induction of CYPs in primary equine hepatocytes employing substances known to induce CYPs in other species. For this purpose, we isolated primary equine hepatocytes following a modified method of Bakala et al. (2003), and established and characterized culture conditions, suitable for induction studies. We investigated three different media to compare morphology, viability, and CYP activity of the cultured cells. We were able to culture the cells under serum-free conditions for at least four days. Rifampicin, a known inducer in humans, increased CYP activity in hepatocytes dose-dependently. However, no induction was measurable after incubations with the known human/rat inducers dexamethasone and phenobarbital in hepatocytes.
In further studies, other equine drugs may be evaluated as CYP inducers with this in vitro system, in order to prevent drug-drug interactions.

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