PUBLICATION

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

Authors
Cornet, C., Calzolari, S., Miñana-Prieto, R., Dyballa, S., van Doornmalen, E., Rutjes, H., Savy, T., D'Amico, D., Terriente, J.
ID
ZDB-PUB-170420-10
Date
2017
Source
International Journal of Molecular Sciences   18(4): (Journal)
Registered Authors
Bartolomé, Carles Cornet, Calzolari, Simone, D'Amico, Leonard, Dyballa, Slyvia, Miñana, Rafael, Savy, Thierry, Terriente, Javier
Keywords
ZeGlobalTox, adverse drug reaction, cardiotoxicity, drug toxicity, hepatotoxicity, high-throughput, neurotoxicity, zebrafish
MeSH Terms
  • Animals
  • Cardiotoxicity
  • Drug Evaluation, Preclinical/methods*
  • Drug-Related Side Effects and Adverse Reactions*
  • Liver/drug effects
  • Liver/pathology
  • Locomotion/drug effects
  • Models, Animal
  • Organ Specificity/drug effects
  • Toxicity Tests*
  • Toxicity Tests, Acute
  • Zebrafish
PubMed
28422076 Full text @ Int. J. Mol. Sci.
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%).
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping