Zebrafish: A Marvel of High-Throughput Biology for 21st Century Toxicology

Abstract

The evolutionary conservation of genomic, biochemical and developmental features between zebrafish and humans is gradually coming into focus with the end result that the zebrafish embryo model has emerged as a powerful tool for uncovering the effects of environmental exposures on a multitude of biological processes with direct relevance to human health. In this review, we highlight advances in automation, high-throughput (HT) screening, and analysis that leverage the power of the zebrafish embryo model for unparalleled advances in our understanding of how chemicals in our environment affect our health and wellbeing.

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance of Intact Zebrafish Embryos Detects Metabolic Changes Following Exposure to Teratogenic Polymethoxyalkenes from Algae

“…Bolstering this potential, the zebrafish has, indeed, been utilized extensively as a toxicological model for a wide array of toxic environmental contaminants, including heavy metals, endocrine disruptors, and various organic pollutants. [7][8][9] In particular, embryonic and subsequent larval stages have proven particularly useful for characterizing teratogenicity (i.e., developmental toxicity). 8,9 With respect to the current study, the zebrafish embryo teratogenicity assay (ZETA) has been specifically used in the investigation of toxic, and specifically, teratogenic metabolites from marine and freshwater algae, including cyanobacteria, 10 and has enabled both characterization of known algal toxins [11][12][13] and identification (through screening, bioassay-guided isolation, and chemical/toxicological characterization) of otherwise unknown toxic metabolites.…”

“…[7][8][9] In particular, embryonic and subsequent larval stages have proven particularly useful for characterizing teratogenicity (i.e., developmental toxicity). 8,9 With respect to the current study, the zebrafish embryo teratogenicity assay (ZETA) has been specifically used in the investigation of toxic, and specifically, teratogenic metabolites from marine and freshwater algae, including cyanobacteria, 10 and has enabled both characterization of known algal toxins [11][12][13] and identification (through screening, bioassay-guided isolation, and chemical/toxicological characterization) of otherwise unknown toxic metabolites. [14][15][16] In one such study, ZETA was used to identify a family of teratogenic secondary metabolites, namely, the polymethoxy-1-alkenes (PMAs), and subsequently demonstrate a taxonomically widespread distribution of these metabolites among both prokaryotic cyanobacteria and eukaryotic algae (i.e., Chlorophyta or green algae).…”

Identification of apoptosis and macrophage migration events in paraquat-induced oxidative stress using a zebrafish model

“…Zebrafish is a useful vertebrate model of human disease with several unique advantages such as (1) small size and high fecundity; (2) transparent embryo and body; (3) short reproductive cycle; (4) rapid development of embryo; (5) facilitates high-throughput toxicity screening; and (6) many genes are functionally conserved with their human orthologues [11,12]. Here we present evidence that the zebrafish is a superior model for the study of PQ-induced oxidative stress.…”

Phenotype anchoring in zebrafish reveals a potential role for matrix metalloproteinases (MMPs) in tamoxifen's effects on skin epithelium

“…This increasingly popular and rapid throughput model can link unique adverse phenotypes with molecular events to elucidate mechanisms of action for toxicants in vivo (Hill et al , 2005; Bugel et al , 2014; Truong et al , 2014). Yet, many pharmaceuticals have not been thoroughly evaluated with this alternative model.…”