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

Tsai Shin Chiang, Kai Chiang Yang, Shu Kai Zheng, Ling Ling Chiou, Wen Ming Hsu, Feng Huei Lin, Guan Tarn Huang, Hsuan Shu Lee

研究成果: 雜誌貢獻文章同行評審

13 引文 斯高帕斯(Scopus)

摘要

A reliable, reproducible, and convenient in vitro platform for drug metabolism determination and toxicity prediction is of tremendous value but still lacking. In the present study, a collection of 24 hepatic transcription factors and nuclear receptors in different combinations were surveyed, and 10 among them were finally selected to induce the expression and enzyme activities of cytochrome P450 (CYP) 3A4, 1B1, and 2C9 in human dermal fibroblasts (HDFs). The expression and activities of these CYPs in the induced HDFs were higher than those in commonly used hepatoma cell lines. High CYP expression and activities could be further enhanced by culturing the induced HDFs either as spheroids or into several kinds of scaffolds, particularly the tri-copolymer scaffold composed of gelatin, chondroitin and hyaluronan. More strikingly, there showed a synergistic effect of seeding and culturing the spheroids into the tri-copolymer scaffold. Scanning electron microscopy and confocal microscopy disclosed well accommodation of these spheroids inside the scaffolds and displayed a high survival rate. Moreover, the spheroid/scaffold constructs could metabolize an anti-hypertension drug nifedipine into oxidized nifedipine, showing their applicability in studying drug metabolism. This study presents a strategy to induce the expression and enzyme activities of critical CYPs in HDFs, and may have potential to establish an in vitro platform to study drug metabolism and to predict the possible human risk of drug toxicity.
原文英語
頁(從 - 到)5187-5197
頁數11
期刊Biomaterials
33
發行號21
DOIs
出版狀態已發佈 - 7月 2012

ASJC Scopus subject areas

  • 生物材料
  • 生物工程
  • 陶瓷和複合材料
  • 材料力學
  • 生物物理學

指紋

深入研究「The prediction of drug metabolism using scaffold-mediated enhancement of the induced cytochrome P450 activities in fibroblasts by hepatic transcriptional regulators」主題。共同形成了獨特的指紋。

引用此