College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Laboratory of Embryo Biotechnology, College of Life Science, Northeast Agricultural University, Harbin, 150030, PR China.
Chem Biol Interact. 2024 Nov 1;403:111258. doi: 10.1016/j.cbi.2024.111258. Epub 2024 Oct 1.
Silicon dioxide (SiO) particles are novel materials with wide-ranging applications across various fields, posing potential neurotoxic effects. This study investigates the toxicological mechanisms of SiO particles of different sizes on murine cerebellar tissue and cells. Six-week-old C57BL/6 mice were orally administered SiO 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 SiO 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 SiO particles. This study elucidates the toxicological mechanism of SiO 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 SiO particles to humans.
二氧化硅（SiO）颗粒是一种新型材料，在各个领域都有广泛的应用，可能具有神经毒性作用。本研究探讨了不同粒径的 SiO 颗粒对小鼠小脑组织和细胞的毒理学机制。将 6 周龄 C57BL/6 小鼠口服给予三种大小（1μm、300nm、50nm）的 SiO 颗粒 21 天，建立体内模型，并在体外培养小鼠小脑星形胶质细胞（C8-D1A 细胞）。采用免疫荧光染色、彗星试验、western blot 和 qRT-PCR 等方法检测氧化应激、DNA 损伤和 PANoptosis 途径的指标。结果表明，SiO 颗粒诱导氧化应激导致 DNA 氧化损伤。异常的 DNA 被 AIM2（黑色素瘤 2 中缺失）识别，激活 PANoptosome 复合物的组装，进而引发 PANoptosis。此外，损伤程度与 SiO 颗粒的大小成反比。本研究阐明了 SiO 颗粒通过 PANoptosis 导致小脑损伤的毒理学机制，拓展了 PANoptosis 在神经毒理学中的研究，并有助于制定更严格的安全标准和保护措施，以降低 SiO 颗粒对人类的潜在毒性风险。
