Silicon dioxide particles induce DNA oxidative damage activating the AIM2-mediated PANoptosis in mice cerebellum

Silicon dioxide (SiO₂) particles are novel materials with wide-ranging applications across various fields, posing potential neurotoxic effects. This study investigates the toxicological mechanisms of SiO₂ particles of different sizes on murine cerebellar tissue and cells. Six-week-old C57BL/6 mice were orally administered SiO₂ particles of three sizes (1 μm, 300 nm, 50 nm) for 21 days to establish an in vivo model, and mice cerebellar astrocytes (C8-D1A cells) were cultured in vitro. Indicators of oxidative stress, DNA damage, and the PANoptosis pathway were detected using methods such as immunofluorescence staining, comet assay, western blotting, and qRT-PCR. The results show that SiO₂ particles induce oxidative stress leading to DNA oxidative damage. The aberrant DNA is recognized by AIM2 (absent in melanoma 2), which activates the assembly of the PANoptosome complex, subsequently triggering PANoptosis. Furthermore, the extent of damage is inversely correlated with the size of SiO₂ particles. This study elucidates the toxicological mechanism of SiO₂ particles causing cerebellar damage via PANoptosis, extending research on PANoptosis in neurotoxicology, and aiding in the formulation of stricter safety standards and protective measures to reduce the potential toxic risk of SiO₂ particles to humans.