The prediction of drug metabolism using scaffold-mediated enhancement of the induced cytochrome P450 activities in fibroblasts by hepatic transcriptional regulators.

摘要: A reliable, reproducible, and convenient in vitro platform for drug metabolism determination toxicity prediction is of tremendous value but still lacking. In the present study, a collection 24 hepatic transcription factors nuclear receptors different combinations were surveyed, 10 among them finally selected to induce expression enzyme activities cytochrome P450 (CYP) 3A4, 1B1, 2C9 human dermal fibroblasts (HDFs). The these CYPs induced HDFs higher than those commonly used hepatoma cell lines. High CYP could be further enhanced by culturing either as spheroids or into several kinds scaffolds, particularly tri-copolymer scaffold composed gelatin, chondroitin hyaluronan. More strikingly, there showed synergistic effect seeding scaffold. Scanning electron microscopy confocal disclosed well accommodation inside scaffolds displayed high survival rate. Moreover, spheroid/scaffold constructs metabolize an anti-hypertension nifedipine oxidized nifedipine, showing their applicability studying metabolism. This study presents strategy critical HDFs, may have potential establish predict possible risk toxicity.