کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10229497 539 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The prediction of drug metabolism using scaffold-mediated enhancement of the induced cytochrome P450 activities in fibroblasts by hepatic transcriptional regulators
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
The prediction of drug metabolism using scaffold-mediated enhancement of the induced cytochrome P450 activities in fibroblasts by hepatic transcriptional regulators
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 33, Issue 21, July 2012, Pages 5187-5197
نویسندگان
, , , , , , , ,