Title:Zebrafish Model in Drug Safety Assessment
Volume: 20
Issue: 34
Author(s): Jyotshna Kanungo, Elvis Cuevas, Syed F. Ali and Merle G. Paule
Affiliation:
Keywords:
Zebrafish, drug, toxicity screening, high throughput assay, neurotoxicity, hepatotoxicity, cardiotoxicity.
Abstract: Over the past decade, zebrafish are being increasingly used in assessing the effects of chemical compounds. Especially, the
embryos and larvae, due to their microscopically small size and optical transparency, are compatible with multi-well microtiter plates for
high throughput screening. Being transparent, they allow for non-invasive visualization of internal organs during early development. The
organization of the genome, the genetic pathways controlling signal transduction and the developmental pattern appear to be significantly
conserved between zebrafish and humans. Major organ systems including the nervous, cardiovascular, digestive and visual systems of
zebrafish are also similar to their mammalian counterparts at the anatomical, physiological and molecular levels. Therefore, zebrafish assays
are ideal for evaluating multiple organ toxicities simultaneously that contrast in vitro assays performed on cultured cells or tissue
explants and organ slices. Although research on zebrafish as a model system began a few decades ago, later studies on zebrafish developmental
biology and developmental genetics resulted in the characterization of a large number of genes involved in vertebrate development
and biological pathways thus establishing zebrafish as a relevant human disease model for research. Recently, zebrafish have become
an attractive vertebrate model for pharmaceutical and toxicological studies. We have outlined in this review some of the toxicological
screens and tools that used zebrafish early life stages, and the efforts made to validate zebrafish assays against mammalian drug
screens.
