Developmental Toxicity of Doxorubicin Hydrochloride in Embryo-larval Stages of Zebrafish

Abstract

Doxorubicin hydrochloride is widely used to treat various types of cancers. Its therapeutic and side effects are well documented. However, the developmental toxicity of doxorubicin has not been previously described. Lethal and sublethal effects on embryo-larval stages of zebrafish in a study of the developmental toxicity of doxorubicin were observed. Zebrafish embryos were exposed to different concentrations (0-100 mg/L) of doxorubicin between 4 and 120 h post fertilization, and zebrafish larvae were exposed to different concentrations (0-200 mg/L) of doxorubicin for 96 h. The markers about the development toxicity of doxorubicin in zebrafish were observed under a stereomicroscope. Higher doxorubicin concentrations mainly caused acute lethal effects, and lower doxorubicin concentrations mainly caused sublethal effects, such as multiple malformations in embryos and larvae. Moreover, with the increase of doxorubicin concentration, the malformation rate increased. The heart rate of embryos was accelerated at lower concentrations of doxorubicin (≤ 10 mg/L) and decelerated at higher concentrations (≥ 25 mg/L). The hatching rate and body length were inhibited at higher concentrations of doxorubicin (≥ 25 mg/L).In conclusion, doxorubicin has serious developmental toxicity and this raises a concern for developmental effects of doxorubicin in clinical practice.