title: A potential model for drug screening by simulating the effect of shear stress in vivo on endothelium.
abstract: The purpose of this paper was to research the potential of a dynamic cell model in drug screening by studying the influence of microvascular wall shear stress on the drug absorption of endothelial cells compared to that in the static state. The cells were grown and seeded on gelatin-coated glass slides and were pretreated with extracts of Salviae miltiorrhizae (200 μg/ml) for 1 h. Then oxidative stress damage was produced by H2O2 (300 μmol/l) for 0.5 h under the 1.5 dyn/cm2 shear stress incorporated in a parallel plate flow chamber. Morphological analysis was conducted with an inverted microscope and image analysis software, and high performance liquid chromatography-mass spectrometry was used for the detection of active compounds. We compared the drug absorption in the dynamic group with that in the static group. In the dynamic model, five compounds and two new metabolite peaks were detected. However, in the static model, four compounds were absorbed by cells, and one metabolite peak was found. This study indicated that there were some effects on the absorption and metabolism of drugs under the microvascular shear stress compared to that under stasis. We infer that shear stress in the microcirculation situation in vivo played a role in causing the differences between drug screening in vitro and in vivo.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, College of Bioengineering, Chongqing University, Chongqing, China.
authors.forename: Yingqian
authors.initials: Y
authors.lastname: Xu
authors.forename: Bochu
authors.initials: B
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Deng
authors.forename: Zerong
authors.initials: Z
authors.lastname: Liu
authors.forename: Liancai
authors.initials: L
authors.lastname: Zhu
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013314:Stress, Mechanical; D053719:Tandem Mass Spectrometry
chemical_list: D017382:Reactive Oxygen Species