Drug absorption related nephrotoxicity assessment on an intestine-kidney chip
Li, Zhongyu1,2,3; Su, Wentao2; Zhu, Yujuan1,2,3; Tao, Tingting2; Li, Dong4; Peng, Xiaojun1; Qin, Jianhua2,3
Indexed BySCI
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
WOS SubjectBiochemical Research Methods ; Biophysics ; Nanoscience & Nanotechnology ; Physics, Fluids & Plasmas
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics ; Science & Technology - Other Topics ; Physics
AbstractDrug 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.
WOS IDWOS:000404340600016
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Document Type期刊论文
Affiliation1.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
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GB/T 7714
Li, Zhongyu,Su, Wentao,Zhu, Yujuan,et al. Drug absorption related nephrotoxicity assessment on an intestine-kidney chip[J]. BIOMICROFLUIDICS,2017,11.
APA Li, Zhongyu.,Su, Wentao.,Zhu, Yujuan.,Tao, Tingting.,Li, Dong.,...&Qin, Jianhua.(2017).Drug absorption related nephrotoxicity assessment on an intestine-kidney chip.BIOMICROFLUIDICS,11.
MLA Li, Zhongyu,et al."Drug absorption related nephrotoxicity assessment on an intestine-kidney chip".BIOMICROFLUIDICS 11(2017).
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