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
-
- Organ Specificity/drug effects
- Locomotion/drug effects
- Toxicity Tests, Acute
- Drug Evaluation, Preclinical/methods*
- Liver/drug effects
- Liver/pathology
- Models, Animal
- Zebrafish
- Animals
- Drug-Related Side Effects and Adverse Reactions*
- Toxicity Tests*
- Cardiotoxicity
- PubMed
- 28422076 Full text @ Int. J. Mol. Sci.
Citation
Cornet, C., Calzolari, S., Miñana-Prieto, R., Dyballa, S., van Doornmalen, E., Rutjes, H., Savy, T., D'Amico, D., Terriente, J. (2017) ZeGlobalTox: An Innovative Approach to Address Organ Drug Toxicity Using Zebrafish. International Journal of Molecular Sciences. 18(4).
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping