A panel of biological tests reveals developmental effects of pharmaceutical pollutants on late stage zebrafish embryos.

in Reproductive Toxicology (2012)

Standard toxicological assays using the zebrafish model system evaluate lethality and teratogenicity upon exposure during the first two days after fertilization. We tested the biological effects of ... [more ▼]

Standard toxicological assays using the zebrafish model system evaluate lethality and teratogenicity upon exposure during the first two days after fertilization. We tested the biological effects of several widely used drugs on zebrafish by acute treatment for 24hours starting at late embryonic stages, between 48 and 72hours post-fertilization. For 4 out of 6 compounds, we observed a higher sensitivity of late stage zebrafish embryos for general toxicity (lethality) compared to younger embryos. Morphological defects such as edema, body curvature, delayed growth, decreased heart rate and locomotion were observed for each of the compounds tested, often at sublethal concentrations. Gene expression studies on a set of four selected genes revealed a specific regulatory pattern for the different compounds tested. Our results allow us to compare various toxicological endpoints and may contribute to the design of a rational high throughput approach using the zebrafish model. [less ▲]

Phenotype Classification of Zebrafish Embryos by Supervised Learning

Conference (2011, September 02)

Leukemic cell xenograft in zebrafish embryo for investigating drug efficacy.

in Haematologica (2011), 96(4), 612-6

Zebrafish were proposed as an alternative to mammalian models to assess the efficacy and toxicity of antileukemic drugs. Due to the limited number of transgenic zebrafish leukemia models, we explored ... [more ▼]

Zebrafish were proposed as an alternative to mammalian models to assess the efficacy and toxicity of antileukemic drugs. Due to the limited number of transgenic zebrafish leukemia models, we explored human leukemic cell xenograft in zebrafish embryos. Human leukemic cell lines and blast cells sorted from patients with acute myelogenous leukemia were injected 48 hours post-fertilization and remained in the circulation of zebrafish embryos for several days without affecting their development. Imatinib and oxaphorines did not demonstrate any toxicity on normal zebrafish embryos and decreased the leukemic burden in animals xenografted with sensitive leukemic cell lines. Two other molecules, all-trans retinoic acid and the translation inhibitor 4EGI-1, demonstrated teratogenic effects at concentrations shown to be efficient in vitro, which precluded investigation of their antileukemic activity in such models. Altogether, xenografted leukemic cells in zebrafish embryos are a pharmacologically relevant model for screening non-teratogenic drugs. [less ▲]