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 1.0μM or higher celastrol were significantly lower. Embryos exposed to 1.0μM celastrol had no blood flow in trunk vessels at 48hpf with a median effect concentration (EC(50)) of 0.94μM. At 72hpf serious edema in pericardial sac was observed in the surviving larvae (hatched from embryos treated with 1.5μM celastrol). Bent tails or hook-like tails were seen as 0.5μM celastrol and the EC(50) for tail malformation was 0.66 μM at 72hpf. The lethal effect of celastrol on zebrafish embryos was dose-dependent and the LC(50) values of celastrol on 1hpf embryos were approximately 1.40μM. These results indicate that celastrol affects the normal development of zebrafish embryo in μM concentrations.
Wang
Sifeng
S
Biology Institute of Shandong Academy of Sciences, Jinan 250014, Shandong, China.
Liu
Kechun
K
Wang
Ximing
X
He
Qiuxia
Q
Chen
Xiqiang
X
D000818:Animals; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D008297:Male; D053978:Pentacyclic Triterpenes; D018675:Toxicity Tests; D029757:Tripterygium / Q000737:chemistry; D014315:Triterpenes / Q000302:isolation & purification / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology*
D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol