Toxic effects of celastrol on embryonic development of zebrafish (Danio rerio)

Celastrol is a terpenoid purified from Tripterygium wilfordii Hook F. As a natural product with pharmacological activities, this compound is a promising candidate for drug development. To provide more information about its toxicity for clinical trials, toxicity assessment of celastrol was conducted with zebrafish model in vivo. 1hour post-fertilization (hpf) embryos were treated with various concentrations of celastrol for 120h. Developmental phenotypes were observed and survival rates were recorded. The results showed that the hatching rates of embryos treated with 1.0 mu M or higher celastrol were significantly lower. Embryos exposed to 1.0 mu M celastrol had no blood flow in trunk vessels at 48hpf with a median effect concentration (EC50) of 0.94 mu M. At 72hpf serious edema in pericardial sac was observed in the surviving larvae (hatched from embryos treated with 1.5 mu M celastrol). Bent tails or hook-like tails were seen as 0.5 mu M celastrol and the EC50 for tail malformation was 0.66 mu M at 72hpf. The lethal effect of celastrol on zebrafish embryos was dose-dependent and the LC50 values of celastrol on 1hpf embryos were approximately 1.40 mu M. These results indicate that celastrol affects the normal development of zebrafish embryo in mu M concentrations.