Samarium Oxide Exposure Induces Toxicity and Cardiotoxicity in Zebrafish Embryos Through Apoptosis Pathway.

Abstract

As a light rare earth element, Sm and Sm₂O₃ are widely used in various fields such as electronics, chemistry, and medicine. Their distribution in the environment, accumulation in biological organisms and exposure through medicinal pathways have attracted increasing public attention. It is crucial to clarify the impact of Sm₂O₃ on human health. In this study, we applied Sm₂O₃ to 24 h post-fertilization (hpf) zebrafish embryos and investigated the toxic effects and mechanisms of Sm₂O₃. The results showed that Sm₂O₃ induced developmental abnormalities in zebrafish embryos, such as prominent pericardial swelling, slight curvature of the spine, and decreased body length. The incidence of abnormalities in zebrafish significantly increased. The scanning electron microscopy and transmission electron microscopy results showed that Sm₂O₃ accumulated in the zebrafish induced the shortening or disappearance of microcrest in zebrafish skin cells. The Lyz-fish system results demonstrated that macrophages migrated to the skin, suggesting that Sm₂O₃ caused damage. Laser confocal microscopy revealed that the heart ventricles of zebrafish embryos exhibited compensatory swelling, ventricular atrophy, and abnormal heart rates. Acridine orange (AO) staining showed obvious green fluorescence. Embryos proteins at 96 hpf were extracted after Sm₂O₃ treatment, revealing that the anti-apoptosis bcl-2 protein decreased with an increase in the Sm₂O₃ concentration. The caspase-3 apoptosis executioner protein also showed concentration-dependent expression, indicating that Sm₂O₃ promotes apoptosis in cardiac tissue cells. DCFH-DA staining showed significant reactive oxygen species (ROS) accumulation in the hearts and brains in zebrafish. In summary, Sm₂O₃ caused ROS accumulation and activated apoptotic pathways in zebrafish embryos, thereby inducing developmental abnormalities and exhibiting biological toxicity. This study demonstrated that 3-day exposure of 24 hpf zebrafish embryos to Sm₂O₃ resulted in pericardial edema, body length reduction, macrophage migration, and shortened micro-ridges of skin cells. Notably, cardiac anomalies included ventricular swelling, atrophy, and arrhythmia, which correlated with elevated ROS levels and apoptotic signals. Mechanistically, Sm₂O₃ promoted apoptosis through downregulation of Bcl-2 and upregulation of caspase-3 expression. These findings collectively reveal that Sm₂O₃ induces developmental toxicity via ROS accumulation and activation of caspase-dependent apoptotic pathways, highlighting its potential biological hazards in early vertebrate development.