Validation of ferroptosis in zebrafish as a reliable model for phenotypic studies

In recent years, ferroptosis has attracted considerable attention as a novel form of cell death. With the deepening of research into its mechanisms, ferroptosis has gained increasing significance. Currently, the vast majority of ferroptosis-related studies are conducted on mice; however, mouse breeding requires a relatively long time, and the cost of gene screening is high. In contrast, zebrafish, as a small-sized vertebrate model organism with a short growth cycle, shares 85% genetic homology with humans.Zebrafish larvae have transparent bodies, which allows for convenient and intuitive observation of their developmental status during the early developmental stage. Would conducting ferroptosis-related experiments on zebrafish larvae be more convenient and efficient than on mice? To verify this hypothesis, the present study treated zebrafish embryos with two ferroptosis inducers (Erastin, FIN56) and ammonium ferric citrate (FAC). The levels of reactive oxygen species (ROS), glutathione (GSH)/oxidized glutathione (GSSG) ratio, somatic cell death, and the expression levels of ferroptosis-related genes and proteins were detected, and differentiated from apoptotic and autophagic indicators. Additionally, ferroptosis-induced impairment of vascular development was observed in transgenic zebrafish with vascular-specific fluorescence. The results of this study indicate that: A ferroptosis model can be successfully established in zebrafish; Ferroptosis significantly inhibits angiogenesis in zebrafish. These findings lay a foundation for future ferroptosis-related research using zebrafish.