ATLA::Alternatives to Laboratory Animals

Volume 27, Number 2

Lack of effect of medium supplementation with pyruvate and hormones on cytochrome P450-mediated activity of rat hepatocytes in primary culture.

ATLA 27, 283-288, March/April 1999

Porntip Wirachwong and Jeffrey R. Fry

School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UG, UK

SUMMARY

The loss of cytochrome P450 (CYP)-dependent activity continues to be a problem in the use of cultured hepatocytes in xenobiotic toxicity studies. It has been reported that the inclusion of pyruvate and various hormones in the culture medium improves the maintenance of various hepatic functions, including that of CYP2C11 mRNA expression. We have studied this further, by investigating the effects of the addition of pyruvate and hormones on various CYP-dependent enzyme activities and on the CYP-dependent toxicity of precocene II in rat hepatocyte cultures. No beneficial effects of this medium supplementation could be demonstrated.

Keywords: hepatocytes, culture, rat, pyruvate, hormones, cytochrome P450, CYP