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Int. J. Mol. Sci. 2017, 18(2), 356; doi:10.3390/ijms18020356

Cell Imaging Counting as a Novel Ex Vivo Approach for Investigating Drug-Induced Hepatotoxicity in Zebrafish Larvae

1
Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, O & N II Herestraat 49-box 824, 3000 Leuven, Belgium
2
Division Pharmaceutical Analysis, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, O & N II Herestraat 49-box 923, 3000 Leuven, Belgium
3
Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, O & N II Herestraat 49-box 921, 3000 Leuven, Belgium
*
Author to whom correspondence should be addressed.
Academic Editor: Juliette Legler
Received: 29 December 2016 / Revised: 27 January 2017 / Accepted: 3 February 2017 / Published: 8 February 2017
(This article belongs to the Special Issue Zebrafish: A Model for Toxicological Research)
View Full-Text   |   Download PDF [5560 KB, uploaded 13 February 2017]   |  

Abstract

Drug-induced liver injury (DILI) is the most common reason for failures during the drug development process and for safety-related withdrawal of drugs from the pharmaceutical market. Therefore, having tools and techniques that can detect hepatotoxic properties in drug candidates at an early discovery stage is highly desirable. In this study, cell imaging counting was used to measure in a fast, straightforward, and unbiased way the effect of paracetamol and tetracycline, (compounds known to cause hepatotoxicity in humans) on the amount of DsRed-labeled hepatocytes recovered by protease digestion from Tg(fabp10a:DsRed) transgenic zebrafish. The outcome was in general comparable with the results obtained using two reference methods, i.e., visual analysis of liver morphology by fluorescence microscopy and size analysis of fluorescent 2D liver images. In addition, our study shows that administering compounds into the yolk is relevant in the framework of hepatotoxicity testing. Taken together, cell imaging counting provides a novel and rapid tool for screening hepatotoxicants in early stages of drug development. This method is also suitable for testing of other organ-related toxicities subject to the organs and tissues expressing fluorescent proteins in transgenic zebrafish lines. View Full-Text
Keywords: hepatotoxicity; drug-induced liver injury (DILI); zebrafish larvae; cell imaging counting; pharmacokinetics hepatotoxicity; drug-induced liver injury (DILI); zebrafish larvae; cell imaging counting; pharmacokinetics
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Nguyen, X.-B.; Kislyuk, S.; Pham, D.-H.; Kecskés, A.; Maes, J.; Cabooter, D.; Annaert, P.; De Witte, P.; Ny, A. Cell Imaging Counting as a Novel Ex Vivo Approach for Investigating Drug-Induced Hepatotoxicity in Zebrafish Larvae. Int. J. Mol. Sci. 2017, 18, 356.

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