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High-content screening technology for studying drug-induced hepatotoxicity in cell models

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Abstract

High-content screening is the application of automated microscopy and image analysis to both cell biology and drug discovery. Over the last decade, this technique has emerged as a useful technology that allows the simultaneous measurement of different parameters at a single-cell level. Hepatotoxicity is a compelling reason for drug nonapprovals and withdrawals. It is recognized that the safety of a compound cannot be based on a single in vitro assay, and existing methods are not predictive of drug-induced toxicity. However, different HCS assays have been recently demonstrated as being powerful for identifying different mechanisms implicated in drug-induced toxicity with high sensitivity and specificity. These assays integrate the data obtained from different cell function indicators and can be easily incorporated into basic screening processes for the safety evaluation and selection of drug candidates; thus, they contribute greatly to lessen the likelihood of drug failure. Exploring the use of cellular imaging technology in drug-induced liver injury by reviewing the different tests proposed provides evidence that this technology has a strong impact on drug discovery.

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Abbreviations

CDF:

5-(6)-Carboxy-2′,7-dichlorofluorescein

CLF:

Cholyl-l-lysyl-fluorescein

DILI:

Drug-induced liver injury

HCS:

High-content screening

MMP:

Mitochondrial membrane potential

MPT:

Mitochondrial permeability transition

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Acknowledgments

The authors wish to thank financial support from the Instituto de Salud Carlos III of the Spanish Ministry of Science and Innovation (PI13/0986) and the ALIVE Foundation. L.T. was a recipient of a Sara Borrell Contract from the “Instituto de Salud Carlos III” of the Spanish Ministry of Economy and Competitiveness.

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Authors and Affiliations

  1. Unidad de Hepatología Experimental, Torre A, Instituto Investigación Sanitaria La Fe (IIS La Fe), Av Fernando Abril Martorell 106, 46026, Valencia, Spain

    Laia Tolosa, M. José Gómez-Lechón & M. Teresa Donato

  2. CIBERehd, FIS, 08036, Barcelona, Spain

    M. José Gómez-Lechón & M. Teresa Donato

  3. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, 46010, Valencia, Spain

    M. Teresa Donato

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  1. Laia Tolosa
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Correspondence to Laia Tolosa.

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Tolosa, L., Gómez-Lechón, M.J. & Donato, M.T. High-content screening technology for studying drug-induced hepatotoxicity in cell models. Arch Toxicol 89, 1007–1022 (2015). https://doi.org/10.1007/s00204-015-1503-z

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  • DOI: https://doi.org/10.1007/s00204-015-1503-z

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