Study on Cardiac and Skeletal Toxicity of Retinoic Acid to Danio rerio at the Early Life Stage / 中国药房

ABSTRACT

OBJECTIVE:To study the cardiac and skeletal toxicity of retinoic acid (RA) in Danio rerio at early life stage. METHODS:Danio rerio embryos of 24 hours post fertilization(hpf)were used as toxicity model and were exposed under medium with various concentrations of RA(0.1,1,10,25,100 μmol/L). The morphology of embryos and larvae hearts were observed 24,48 h after exposed. LC50 was calculated. Danio rerio larvae of 4 days post fertilization (dpf) were used as skeletal deformity model and were exposed with a series of RA at various concentration(0.1,1,10,25,50μmol/L). They were sacrificed 5 d later, and then Danio rerio skeleton were fixed for staining with alizarin red. The microscopic was used to observe the difference of stained skeleton area. RESULTS:RA caused significant adverse effects on hatching capabilities of Danio rerio embryos,and the ob-vious malformation features were produced during the culture process. 1-100 μmol/L RA could cause heart malformation in Danio rerio embryos and larvae,and the main heart malformation characteristics included heart linearization,pericardial edema,yolksa-cedema,hemocytes accumulation incardiac region. 100 μmol/L RA could inhibit the hatching capabilities of Danio rerio embryos, and caused lethal effects on embryos and larvae. The LC50 were 36.44,23.69 μmol/L after exposed for 24,48 h. 0.1-50 μmol/L RA induced vertebral column sclerotization of Danio rerio embryos and larvae in advance,which was positively associated with the con-centration of RA. CONCLUSIONS:RA can cause cardiac and skeletal toxicity in Danio rerio embryo and larvae,which is positive-ly associated with the concentration of RA.