The use of in vivo zebrafish assays in drug toxicity screening

Abstract

Anecdotal evidence has long suggested that zebrafish may be a good model to predict toxicity of human drugs. As summarized in this review, several groups have recently conducted systematic evaluations of zebrafish toxicity end points using large numbers of pharmacologically relevant compounds. Assays of particular interest include those for cardiotoxicity, ototoxicity, seizure liability, developmental toxicity and gastrointestinal motility. Results suggest that zebrafish assays can attain an acceptable level of predictivity, ranging from “sufficient” (65 – 75% predictivity) to “good” (75 – 85% predictivity) based on guidelines established for novel in vitro tests by the European Centre for the Validation of Alternative Methods. Further validation will probably be required to definitely establish zebrafish as a standard model for toxicity testing.

Keywords::

• cardiotoxicity
• developmental toxicology
• gastrointestinal motility
• hERG
• ototoxicity
• QT prolongation
• safety pharmacology
• seizure liability
• toxicology
• zebrafish

Acknowledgements

The authors thank N Sawczuk and T Baranowski and E Bush for their comments on the manuscript.