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Int J Mol Sci. 2017 Apr 19;18(4). pii: E864. doi: 10.3390/ijms18040864.

ZeGlobalTox: An Innovative Approach to Address Organ Drug Toxicity Using Zebrafish.

Author information

1
ZeClinics SL, PRBB (Barcelona Biomedical Research Park), 08003 Barcelona, Spain. carles.cornet@zeclinics.com.
2
ZeClinics SL, PRBB (Barcelona Biomedical Research Park), 08003 Barcelona, Spain. simone.calzolari@zeclinics.com.
3
ZeClinics SL, PRBB (Barcelona Biomedical Research Park), 08003 Barcelona, Spain. rafael.minana@zeclinics.com.
4
ZeClinics SL, PRBB (Barcelona Biomedical Research Park), 08003 Barcelona, Spain. sylvia.dyballa@zeclinics.com.
5
Pivot Park Screening Centre (PPSC), Kloosterstraat 9, 5349AB OSS, The Netherland. els.vandoornmalen@ppscreeningcentre.com.
6
Pivot Park Screening Centre (PPSC), Kloosterstraat 9, 5349AB OSS, The Netherland. helma.rutjes@ppscreeningcentre.com.
7
Multilevel Dynamics in Morphogenesis Unit, USR3695 CNRS, 91190 Gif sur Yvette, France. thierry.savy@polytechnique.edu.
8
ZeClinics SL, PRBB (Barcelona Biomedical Research Park), 08003 Barcelona, Spain. davide.damico@zeclinics.com.
9
ZeClinics SL, PRBB (Barcelona Biomedical Research Park), 08003 Barcelona, Spain. javier.terriente@zeclinics.com.

Abstract

Toxicity is one of the major attrition causes during the drug development process. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind the retirement of drugs in clinical phases and post market withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the toxicity and efficacy of novel drugs. This animal model has, from early developmental stages, fully functional organs from a physiological point of view. Thus, drug-induced organ-toxicity can be detected in larval stages, allowing a high predictive power on possible human drug-induced liabilities. Hence, zebrafish can bridge the gap between preclinical in vitro safety assays and rodent models in a fast and cost-effective manner. ZeGlobalTox is an innovative assay that sequentially integrates in vivo cardio-, neuro-, and hepatotoxicity assessment in the same animal, thus impacting strongly in the 3Rs principles. It Reduces, by up to a third, the number of animals required to assess toxicity in those organs. It Refines the drug toxicity evaluation through novel physiological parameters. Finally, it might allow the Replacement of classical species, such as rodents and larger mammals, thanks to its high predictivity (Specificity: 89%, Sensitivity: 68% and Accuracy: 78%).

KEYWORDS:

ZeGlobalTox; adverse drug reaction; cardiotoxicity; drug toxicity; hepatotoxicity; high-throughput; neurotoxicity; zebrafish

PMID:
28422076
PMCID:
PMC5412445
DOI:
10.3390/ijms18040864
[Indexed for MEDLINE]
Free PMC Article

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