Antimony trioxide nanoparticles promote ferroptosis in developing zebrafish (Danio rerio) by disrupting iron homeostasis.

The widespread use of antimony trioxide (ATO) and ATO nanoparticles (nATO) has led to increasing ecological and health risks. However, there is relatively insufficient research on the aquatic ecotoxicology of nATO. This study revealed that nATO affects the development of zebrafish embryos and mainly induces ferroptosis through the dissolution of Sb(III). The size of nATO ranged from 50 to 250 nm, and it generated free radicals in water. It can be ingested and accumulate in zebrafish larvae and affects normal development. Compared with those in the control group, the levels of reactive oxygen species (ROS), cell apoptosis, mitochondrial damage and iron content in the group exposed to high concentrations of nATO were increased. The transcriptomics results indicated that nATO significantly altered the expression levels of key genes related to glutathione metabolism and ferroptosis. Quantitative polymerase chain reaction consistently demonstrated the reliability of the transcriptome data and revealed that nATO induced ferroptosis by disrupting iron homeostasis and the key factor is the dissolution of Sb(III). Furthermore, ferrostatin-1, an inhibitor of ferroptosis, decreased the levels of ROS, apoptosis and mitochondrial damage induced by nATO, which further prove that nATO can promote ferroptosis. This work deepens the understanding of the ecological toxicological effects of nATO in aquatic environments and its mechanisms, which is highly important for the development of antimony management strategies.