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Assessment of hepatic metabolism-dependent nephrotoxicity on an organs-on-a-chip microdevice
Li, Zhongyu1,3,4; Jiang, Lei1; Zhu, Yujuan1,3; Su, Wentao1; Xu, Cong1,3; Tao, Tingting1,3; Shi, Yang1; Qin, Jianhua1,2,3
KeywordMicrofluidics Drug Testing Hepatic Metabolism Nephrotoxicity Organs-on-a-chip
Source PublicationTOXICOLOGY IN VITRO
2018-02-01
ISSN0887-2333
DOI10.1016/j.tiv.2017.10.005
Volume46Pages:1-8
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectToxicology
WOS Research AreaToxicology
WOS KeywordPOROUS MEMBRANES ; DRUG DISCOVERY ; TOXICITY ; LIVER ; IFOSFAMIDE ; SYSTEMS ; CELLS ; TECHNOLOGIES ; BIOMARKERS ; TOXICOLOGY
AbstractDrug-induced nephrotoxicity is one of the most frequent adverse events in pharmacotherapy. It has resulted in numerous clinical trial failures and high drug development costs. The predictive capabilities of existing in vitro models are limited by their inability to recapitulate the complex process of drug metabolism at the multi-organ level in vivo. We present a novel integrated liver-kidney chip that allows the evaluation of drug-induced nephrotoxicity following liver metabolism in vitro. The liver-kidney chip consists of two polydimethylsiloxane layers with compartmentalized micro-channels separated by a porous membrane. Hepatic and renal cells were co-cultured in separate micro-chambers on a single chip. Ifosfamide and verapamil were used as model drugs, and their metabolites produced by hepatic metabolism were identified using mass spectrometry, respectively. The metabolites triggered significantly distinct nephrotoxic effects as assessed by cell viability, lactate dehydrogenase leakage and permeability of renal cells. This in vitro liver-kidney model facilitates the characterization of drug metabolism in the liver as well as the assessment of subsequent nephrotoxicity in a single assay. Obviously, this multi-organ platform is simple and scalable, and maybe widely applicable to the evaluation of drug metabolism and safety during the early phases of drug development.
Language英语
WOS IDWOS:000422811300001
PublisherPERGAMON-ELSEVIER SCIENCE LTD
Citation statistics
Cited Times:4[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/168479
Collection中国科学院大连化学物理研究所
Corresponding AuthorQin, Jianhua
Affiliation1.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian 116023, Peoples R China
2.Chinese Acad Sci, Ctr Excellence Brain Sci & Intelligence Technol, Shanghai, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China
Recommended Citation
GB/T 7714
Li, Zhongyu,Jiang, Lei,Zhu, Yujuan,et al. Assessment of hepatic metabolism-dependent nephrotoxicity on an organs-on-a-chip microdevice[J]. TOXICOLOGY IN VITRO,2018,46:1-8.
APA Li, Zhongyu.,Jiang, Lei.,Zhu, Yujuan.,Su, Wentao.,Xu, Cong.,...&Qin, Jianhua.(2018).Assessment of hepatic metabolism-dependent nephrotoxicity on an organs-on-a-chip microdevice.TOXICOLOGY IN VITRO,46,1-8.
MLA Li, Zhongyu,et al."Assessment of hepatic metabolism-dependent nephrotoxicity on an organs-on-a-chip microdevice".TOXICOLOGY IN VITRO 46(2018):1-8.
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