Comparison of Toxicity of General Anesthetics in the Fetus or Neonate Using Zebrafish Embryo

초록

Background and Objectives: Exposure to general anesthetics in the fetus or neonate has been associated with toxicity, such as malformations and reduced intellectual development. Zebrafish is a vertebrate animal model that has high genetic and physiological similarities to humans, and allows for rapid and large-scale research compared to mammalian models. It has recently been in the spotlight as an alternative animal model for disease and toxicity research. Our goal was to compare the toxicity of general anesthetics during fetal period using zebrafish embryos. Methods: Zebrafish embryos at 2 hours postfertilization (hpf) were exposed to control, etomidate 10 μM, etomidate 100 μM, dexmedetomidine 10 μM, dexmedetomidine 100 μM, thiopental sodium 10 μM, thiopental sodium 100 μM, remimazolam 80 μM, or remimazolam 800 μM for 3 days. In cases where toxicity was low and dimicult to evaluate, the concentration was increased to determine whether it was similar to other agents. There were 20 embryos in one group and this experiment was repeated 3 times. Starting at 24 hpf, all embryos were observed every 24 hours for 3 days, mortality and hatching rates were analyzed. Results: Remimazolam showed the lowest mortality of about 8% even when the concentration was increased to 800uM. Thiopental sodium 100μM, etomidate 100μM, and dexmedetomidine 100 μM showed 90% motrality, but unlike dexmedetomidine 100 μM, thiopental sodium 100μM and etomidate 100μM were measured at a low hatching rate of 10%. The degree of deformity after hatching was more severe in etomidate 100μM. Discussion and Conclusion: This study showed that general anesthetics lead to hatching defects in zebrafish embryos. Relatively, remimazolam was evaluated as having low toxicity as it showed a low mortality rate even at high concentrations. The dimerence in hatching rate between etomidate 100 μM and thiopental sodium100 μM was significantly lower, so further research is needed.