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Updated: Jul 17, 2025
Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
Published on: August 25, 2019
Toxic effects of sirolimus and everolimus on the development and behavior of zebrafish embryos
Zixin Zhang1, Tong Qiu1, Jiangyuan Zhou1
1Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China.
Abstract:
Sirolimus and everolimus have been widely used in children. These mammalian target of rapamycin (mTOR) inhibitors have shown excellent efficacy not only in organ transplant patients as immunosuppressive agents but also in patients with some other diseases. However, whether mTOR inhibitors can affect the growth and development of children is of great concern. In this study, using zebrafish models, we discovered that sirolimus and everolimus could slow the development of zebrafish, affecting indicators such as survival, hatching, deformities, body length, and movement. In addition to these basic indicators, sirolimus and everolimus had certain slowing effects on the growth and development of the nervous system, blood vessels, and the immune system. These effects were dose dependent. When the drug concentration reached or exceeded 0.5 μM, the impacts of sirolimus and everolimus were very significant. More interestingly, the impact was transient. Over time, the various manifestations of experimental embryos gradually approached those of control embryos. We also compared the effects of sirolimus and everolimus on zebrafish, and we revealed that there was no significant difference between these drugs in terms of their effects. In summary, the dose of sirolimus and everolimus in children should be strictly controlled, and the drug concentration should be monitored over time. Otherwise, drug overdosing may have a certain impact on the growth and development of children.
Insights
Sirolimus and everolimus, mammalian target of rapamycin (mTOR) inhibitors, can slow zebrafish development, impacting survival, growth, and organ systems. These effects are dose-dependent but transient, suggesting careful pediatric dosing is crucial.
Area of Science:
- Developmental Biology
- Pharmacology
- Toxicology
Background:
- Sirolimus and everolimus are widely used mammalian target of rapamycin (mTOR) inhibitors in pediatric patients for immunosuppression and other conditions.
- Concerns exist regarding the potential impact of these mTOR inhibitors on pediatric growth and development.
Purpose of the Study:
- To investigate the effects of sirolimus and everolimus on the growth and development of zebrafish.
- To determine the dose-dependency and transient nature of any observed effects.
- To compare the impact of sirolimus versus everolimus on zebrafish development.
Main Methods:
- Zebrafish embryos were exposed to varying concentrations of sirolimus and everolimus.
- Developmental indicators including survival, hatching, deformities, body length, and movement were assessed.
- Effects on the nervous, vascular, and immune systems were evaluated.
Main Results:
- Sirolimus and everolimus significantly slowed zebrafish development, affecting survival, hatching, body length, and movement in a dose-dependent manner.
- Adverse effects on nervous, vascular, and immune system development were observed at concentrations ≥ 0.5 μM.
- The observed developmental impacts were transient, with zebrafish gradually recovering over time. No significant difference was found between sirolimus and everolimus.
Conclusions:
- Pediatric dosing of sirolimus and everolimus requires strict control and monitoring to prevent potential impacts on growth and development.
- Transient developmental effects underscore the importance of therapeutic drug monitoring to avoid potential long-term consequences.
