Differential Neurodevelopmental Toxicity of Propofol and Fospropofol: Mechanistic Insights and Potential Clinical Implications—A Zebrafish Model Study

Propofol and fospropofol are used in pediatric surgical anesthesia, but their comparative developmental safety remains uncertain. In this study, zebrafish embryos were exposed to equianesthetic concentrations of propofol or fospropofol. Embryonic survival, hatching, malformation, and post-anesthesia motor behavior were assessed. RNA sequencing and molecular docking were performed to explore potential molecular mechanisms. Fospropofol exhibited lower developmental toxicity than propofol, as shown by the higher survival and hatching rates and a lower malformation rate. Comparative toxicogenomic analysis revealed distinct molecular pathways and candidate targets that may underlie these differential effects. Collectively, these zebrafish data suggest a favorable developmental safety profile for fospropofol and underscore the need for dose optimization and monitoring in pediatric anesthetic management; validation in mammalian models and controlled human studies is further warranted.