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题名: Drug absorption related nephrotoxicity assessment on an intestine-kidney chip
作者: Li, Zhongyu1, 2, 3;  Su, Wentao2;  Zhu, Yujuan1, 2, 3;  Tao, Tingting2;  Li, Dong4;  Peng, Xiaojun1;  Qin, Jianhua2, 3
刊名: BIOMICROFLUIDICS
发表日期: 2017-05-01
DOI: 10.1063/1.4984768
卷: 11
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine ;  Physical Sciences
类目[WOS]: Biochemical Research Methods ;  Biophysics ;  Nanoscience & Nanotechnology ;  Physics, Fluids & Plasmas
研究领域[WOS]: Biochemistry & Molecular Biology ;  Biophysics ;  Science & Technology - Other Topics ;  Physics
英文摘要: Drug absorption in the intestine is tightly related to drug-induced nephrotoxicity, which is a relatively common side effect in clinical practice. It highlights a great need to develop predictive models with high accuracy in the early stage during new drug discovery and development. Herein, we presented a novel intestine-kidney chip, which recapitulated drug absorption in the intestine and its resultant drug toxicity on the kidney. This work aims to provide an integrated tool for accurate assessment of drug absorption-related nephrotoxicity in vitro. A microfluidic device with multi-interfaces was designed, which facilitated the co-culture of the intestinal and glomerular endothelial cells in compartmentalized micro-chambers. Thus, drug absorption and following nephrotoxicity could be explored in a single assay based on the formation of the intact intestine function on the chip. Specifically, we adopt digoxin (DIG) as a model drug combined with colestyramine (COL) or Verapamil (VER), which significantly influence DIG absorption in the intestine. Different degrees of nephrotoxicity under drug combinations were further observed on the chip, including cell apoptosis, cell viability, and lactate dehydrogenase leakage. These features were consistent with the variance of DIG absorption by the intestinal cells. In agreement with clinical observations, our data demonstrated that DIG-induced nephrotoxicity was enhanced combined with VER but weakened with COL. All of these findings suggest that the established microdevice might provide a useful and cost-effective platform in vitro for testing drug absorption and nephrotoxicity in preclinical trials during new drug development. Published by AIP Publishing.
关键词[WOS]: ON-A-CHIP ;  IN-VITRO ;  POROUS MEMBRANES ;  CELL-CULTURE ;  MODELS ;  TOXICITY ;  SYSTEMS ;  ORGANS ;  MICROENVIRONMENT ;  METABOLISM
语种: 英语
WOS记录号: WOS:000404340600016
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/152131
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Dalian Univ Technol, Coll Chem, Dalian 116024, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian 116023, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Dalian Municipal Women & Childrens Med Ctr, Dalian 116024, Peoples R China

Recommended Citation:
Li, Zhongyu,Su, Wentao,Zhu, Yujuan,et al. Drug absorption related nephrotoxicity assessment on an intestine-kidney chip[J]. BIOMICROFLUIDICS,2017,11.
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