Key result
Doxorubicin exposure causes high-dose lethality and low-dose malformations with altered heart rates in zebrafish.
Why the study?
The developmental toxicity of doxorubicin hydrochloride has not been previously described despite its widespread use and known therapeutic and side effects.
Does doxorubicin exposure cause developmental toxicity in embryo-larval stages of zebrafish?
Does doxorubicin exposure cause developmental toxicity in embryo-larval stages of zebrafish?
Doxorubicin demonstrates significant developmental toxicity in a zebrafish model, highlighting potential risks for developmental effects in clinical settings.
Answers are grounded in this paper and cite their sources.
Indicates potential developmental risks with doxorubicin; leaves open translation to human embryos and requires mammalian validation.
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.
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Chang et al. (2014) studied Developmental toxicity. Doxorubicin hydrochloride vs. 0 mg/L was evaluated on Lethal and sublethal effects (malformations, heart rate, hatching rate, body length). Doxorubicin exposure in zebrafish caused acute lethal effects at higher concentrations and sublethal effects including malformations and altered heart rates at lower concentrations.
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