Model validation and evaluation of developmental toxicity of five drugs using zebrafish embryos / 中国药理学通报

ABSTRACT

Aim To explore the toxicity and safety of five kinds of known positive drugs, cyclophosphamide, acetyl salicylic acid, tetracycline hydrochloride, dexa-methasone acetate and azacitidine, using zebrafish em-bryos. Methods We selected normally developed 4 hpf zygote, and used water bath infecting method to add the drug to the artificial seawater. Each drug had five concentrating groups, a separate control group and solvent control group. We observed the dead zebrafish embryos after 120 hpf drugs, counted the number of deaths and deformities of zebrafish embryos, and cal-culated mortality abnormal rate, the median lethal con-centration (LC50 ), concentration for 50% of maximal effect (EC50 ), therapeutic index (TI) under 120 hpf condition. We also used the formula TI = LC50 / EC50 to calculate positive drug therapeutic index. Based on measured LC50 we calculated most nonlethal concentra-tion (MNLC) of each drug setting, namely 1 / 10 MN-LC, 1 / 3 MNLC, MNLC,LC10 four concentration, tha-lidomide as a positive control, vitamin C as a negative control, artificial seawater as control, 0. 5% DMSO as solvent control. Put in 28. 5 ℃ environment for 120 hours,embryo development was observed daily for de-velopmental state,mortality,deforming rate and abnor-mal condition. Results The result of five drugs LC50 in descending order cyclophosphamide > azacitidine> tetracycline hydrochloride > acetylsalicylic acid >dexamethasone acetate. EC50 in descending order cy-clophosphamide > tetracycline hydrochloride > azaciti-dine > acetylsalicylic acid > dexamethasone acetate. The TI values of cyclophosphamide, acetyl salicylic acid, tetracycline hydrochloride, dexamethasone ace-tate, azacitidine were 1. 92, 1. 11, 1. 05, 1. 44, 2. 99, respectively. Conclusion Zebrafish embryo model can be used in the preliminary evaluation of drugs, and the study of early developmental toxicity and safety.