Zebrafish assays for drug toxicity screening

Abstract

Zebrafish are vertebrate organisms that are of growing interest for preclinical drug discovery applications. Zebrafish embryos develop most of the major organ systems present in mammals, including the cardiovascular, nervous and digestive systems, in < 1 week. Additional characteristics that make them advantageous for compound screening are their small size, transparency and ability to absorb compounds through the water. Furthermore, gene function analysis with antisense technology is now routine procedure. Thus, it is relatively simple to assess whether compounds or gene knockdowns cause toxic effects in zebrafish. Assays are being developed to exploit the unique characteristics of zebrafish for pharmacological toxicology. This review discusses assays that may be used to assess invivo toxicity and provides examples of compounds known to be toxic to humans that have been demonstrated to function similarly in zebrafish.

Keywords::

• cardiotoxicity
• cytochrome P450
• neurotoxicity
• teratogenesis
• zebrafish

Acknowledgements

The author thanks the following people for commenting on this manuscript: Drs A Bahinski, T Baranowski, E Blomme, T Doan, J Hartke, R Garippa, C MacRae and R Peterson. DrS Lin is thanked for the gift of the TG(cmlc2:GRCFP) transgenic fish shown in Figure 1.