Lanthanum oxide nanoparticles induce AHR-mediated hepatotoxicity in zebrafish via oxidative stress and metabolic dysregulation

Lanthanum oxide nanoparticles (La₂O₃ NPs) are extensively utilized in industrial, medical, and technological fields and are increasingly infiltrating aquatic ecosystems; however, their ecotoxicological impacts remain poorly understood. This study used zebrafish to elucidate the hepatotoxicity induced by La₂O₃ NPs through oxidative stress, apoptosis, and metabolic dysregulation. Exposure to La₂O₃ NPs triggered reactive oxygen species (ROS) overload in the liver of larvae, provoking oxidative damage and hepatocyte apoptosis. Transcriptomic analysis revealed altered expression of genes critical for liver function, including cytochrome P450 enzymes, implicating activation of the aryl hydrocarbon receptor (ahr) signaling pathway as a key mechanistic driver. Following 90 days of chronic exposure, the La content in the liver of zebrafish exposed to 10 mg/L La₂O₃ NPs reached as high as 5.637 ± 0.188 μg/g, and histopathological evaluation confirmed that La₂O₃ NPs accumulation induces hepatic vacuolation and elevated ALT/AST levels, underscoring structural and functional hepatic impairments. Furthermore, the liver area in the 10 mg/L exposure group was reduced by 39 % compared to the control group, manifesting a small liver phenotype. La₂O₃ NPs promote lipid and glycogen accumulation in the liver, inhibit enzyme activity, and disrupt lipid metabolism genes (ppar-α and cpt1aa) and glucose metabolism genes (hk1, gys2, and pdhx), indicating profound metabolic dysfunction. This study provides the first evidence linking La₂O₃ NPs to ahr-mediated hepatotoxicity in aquatic organisms, highlighting their capacity to impair liver development, induce metabolic disorders, and bioaccumulate in zebrafish. These findings emphasize the urgent need for environmental monitoring and regulatory frameworks to mitigate ecological risks posed by rare earth nanomaterials, safeguarding aquatic health and trophic integrity.