Induction of CYP3A isoforms in cultured precisioncut human liver slices

Abstract

1. The effect of rifampicin on cytochrome P450 isoforms in the CYP1A and CYP3A subfamilies has been studied in 72-h cultured precision- cut human liver slices. 2. In cultured human liver slices 50 μM rifampicininducedtestosterone 6 β-hydroxylase activity, but had no effect on 7-ethoxyresorufin O-deethylase and 7-methoxyresorufin O-demethylase activities. 3. Western immunoblottingof liver slice microsomeswas performed with antibodiesto rat CYP1A2 and human CYP3A4. Compared with control (dimethyl sulphoxide only treated) liver slice microsomes,rifampicinincreased levels of CYP3A4 but had no effect on CYP1A2. 4. These results demonstrate that rifampicin induces CYP3A isoforms, but not CYP1A2,in cultured human liver slices. Some variability in the magnitudeof induction by rifampicin was observed in the six human liver samples examined. 5. These results demonstrate that cultured human liver slices may be used to evaluate the effects of xenobiotics on CYP3A isoforms.