Safety Evaluation of Jiaotaiwan Based on Zebrafish Model / 中国实验方剂学杂志

ABSTRACT

Objective:To take zebrafish embryo as the research object, in order to investigate the development toxicity, cardiotoxicity, liver toxicity and kidney toxicity of water extract of Jiaotaiwan (JTW) on zebrafish embryo. Method:Zebrafish embryos with normal development at 12 h (hpf) after fertilization were selected as model animals for the growth and cardiotoxicity experiments. The embryos were treated with 125, 250, 500 mg·L-1 of JTW water extracts, and the effects of the drugs on the heart rate and morphology of the embryos and LD50 were observed at 72 h (hpf) after fertilization. Zebrafish embryos with normal development at 72 h (hpf) after fertilization were used as model animals for the liver and kidney toxicity experiments. The embryos were treated with 125，250，500 mg·L-1 of JTW water extracts, and the effect of the drugs on morphological changes, Alanine aminotransferase(ALT), Aspartate aminotransferase (AST) activity, and creatinine content of the larvae and LD50 were observed at 72 d (dpf) after fertilization. Result:The zebrafish embryos in control group developed normally, the heart was well developed, and the heartbeat was even and powerful. The LD50 of JTW water extract on zebrafish embryos for 72 h was 1 023 mg·L-1. Compared with the embryos in the control group, 250，500 mg·L-1 treatment groups in the development toxicity had a smaller head, shorter body lengths (P<0.05), and decreased eye size (P<0.05). Compared with the control group embryos, the pericardial edema was observed in the 500 mg·L-1 group, the heart rate was significantly decreased in the 250，500 mg·L-1 JTW water extract groups (P<0.01), the atrial and ventricular areas were significantly reduced (P<0.05), the distance of SV-BA became significantly larger (P<0.05), the distance of AV channel became significantly larger (P<0.01), and the in-flow distance was significantly shorter (P<0.01). In the acute toxicity experiment, the LD50 of JTW water extract for zebrafish larvae for 72 h was 1 067 mg·L-1. Compared with control group, JTW water extract significantly reduced ALT activity in zebrafish larvae (P<0.05). Conclusion:This experiment found that JTW has an obvious toxicity in embryonic development, which is mainly manifested as delayed growth and severe cardiotoxicity. Great attention shall be paid to clinical administration to pregnant women, lactating women and patients with heart disease.