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Updated: May 27, 2025
Small Molecule Screening and Toxicity Testing in Early-stage Zebrafish Larvae
Published on: March 7, 2025
Toxic effects of prolonged propofol exposure on cardiac development in zebrafish larvae
Shaojie Qian1, Huizi Liu1, Hanwei Wei1
1Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Insights
Propofol anesthesia during pregnancy can harm fetal heart development. This study shows propofol negatively impacts zebrafish heart structure and function, identifying agxt2 as a potential toxicity target.
Area of Science:
- Developmental biology
- Cardiovascular research
- Toxicology
Background:
- Propofol is a common intravenous anesthetic used during pregnancy.
- It readily crosses the placental barrier, posing potential risks to fetal development.
- Fetal heart development may be particularly vulnerable to anesthetic exposure.
Purpose of the Study:
- To investigate the effects of propofol on the developing zebrafish heart.
- To assess propofol's impact on cardiac structure and function.
- To identify potential molecular targets of propofol-induced cardiotoxicity.
Main Methods:
- Zebrafish embryos were exposed to varying concentrations of propofol.
- Cardiac structure and function (heart rate) were evaluated.
- In vitro cardiomyocyte viability and migration assays were performed.
- Transcriptomic sequencing identified potential drug targets.
Main Results:
- Propofol exposure decreased zebrafish hatching and survival rates, increasing deformities.
- Observed cardiac abnormalities included enlarged cavities and thinned myocardial walls.
- Propofol reduced heart rate, cardiomyocyte viability, and migration, while increasing apoptosis.
- Transcriptome analysis identified agxt2 as a potential target.
Conclusions:
- Propofol adversely affects developing zebrafish heart structure and function.
- The gene agxt2 is identified as a potential mediator of propofol's cardiotoxic effects.
- Findings highlight the need for further investigation into anesthetic risks during pregnancy.
Background:
Propofol, commonly used as an intravenous anesthetic during pregnancy, can easily penetrate the placental barrier, potentially affecting fetal heart development. This study aims to investigate propofol's impact on developing zebrafish heart structure and function, and identify potential drug targets.
Methods:
Zebrafish embryos were exposed to different concentrations of propofol (0.5, 1, and 5 mg/L) to observe changes in zebrafish larval heart structure and function (heart rate). In vitro cell experiments were conducted to assess the effects of propofol at different concentrations on cardiomyocyte viability and migration. Transcriptomic sequencing was utilized to identify and validate potential drug targets associated with propofol-induced cardiac toxicity.
Results:
The results demonstrate that propofol dose-dependently reduces the hatching and survival rates of zebrafish larvae, while increasing the rate of deformities. Transgenic green fluorescent zebrafish larvae exposed to propofol exhibit enlarged cardiac cavities, and HE staining reveals thinning of the myocardial wall. Additionally, propofol-treated zebrafish larvae show a decrease in heart rate. We also assess the impact of propofol on myocardial cell function, showing decreased cell viability, reduced migration function, and increased apoptosis. Finally, transcriptome sequencing analysis and differential gene co-expression network analysis identify agxt2 as a potential target of propofol-induced cardiac toxicity.
Conclusion:
In conclusion, our study indicates that propofol alters the structure and function of the developing zebrafish heart, with the mitochondrial-related gene agxt2 possibly being a target of its pharmacological effects.
