<i>In Vitro</i> Assessment of Drug-Induced Liver Injury Using Cell-Based Models: A Review

نویسندگان

چکیده

Drug-induced liver injury (DILI) is the reason for 15–18% of medicinal product recalls from market. Since interspecies differences often limit relevance standard non-clinical tests in vivo , a promising alternative to develop cell-based vitro methods. The aim study was review current advances cell modelling identification DILI. In mechanistic studies DILI require cells that exhibit activity specific hepatic metabolising enzymes and transporters. This article reviews main cultures (primary human hepatocytes, immortal lines, stem cell-derived hepatocyte-like cells, co-cultures hepatocytes non-parenchymal cells) their configurations. optimisation systems directed towards enhancing viability, functionality, compositional configurational complexity, thus bringing them closer models. Potential causes include chemically reactive metabolites, oxidative stress, mitochondrial damage, intracellular accumulation toxic bile acids resulting transporter inhibition, adaptive immune system activation. Accordingly, rely on various methods, including innovative technologies acquisition, storage, analysis large datasets (e.g. high-content screening, transcriptomics, proteomics, metabolomics). Cell models are applicable both studies. Currently, most omics, complex co-culture models, organ-on-a-chip systems.

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1Office of Computational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA 2Center of Pharmacology and Toxicology, Hannover Medical School, Hannover, Germany 3Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA 4Division of Bioinformatics and Biostatistics, National Center for Toxicological Research,...

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ژورنال

عنوان ژورنال: ???????????? ? ???? ??????????????

سال: 2023

ISSN: ['2312-7821', '2619-1164']

DOI: https://doi.org/10.30895/2312-7821-2023-11-2-351