Immunotoxicity of silica nanoparticles and the potential role of vitamin C

Abstract

BACKGROUND: The increasing use of silica nanoparticles (SiNPs) has raised concerns about their hazards to human health. However, immunotoxic effect remains insufficiently explored. OBJECTIVE: To assess: the immunotoxicity of orally administered SiNPs; role of inflammation, apoptosis, autophagy; and the protective role of vitamin C. METHODS: Eighty Sprague Dawley rats were randomly divided into four groups: control, SiNPs, vitamin C, and combined SiNPs + vitamin C. SiNPs and vitamin C were orally administered for 90 days. Immunotoxicity was assessed using flow cytometry for lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, CD16+, CD56+), cytokine assays for IL-1β, IL-6, and IFN-γ, histopathological evaluation of bone marrow, and immunohistochemistry for Caspase-3 (apoptosis) and Beclin-1 (autophagy). RESULTS: SiNPs exposure caused significant elevations in CD3+, CD4+, CD8+, CD16+, and CD19+ cells and a reduction in CD56+ cells. Serum cytokine levels increased markedly in the SiNPs group than controls (107.7 ± 13.7 pg/mL, 22.9 ± 6.7 pg/mL, 13.5 ± 1.6 pg/mL vs. 53.5 ± 6.5 pg/mL, 9.38 ± 1.6 pg/mL, 6.7 ± 0.8 pg/mL respectively) showing a 2.01-fold rise in IL-1β and IFN-γ and a 2.44-fold rise in IL-6. Co-administration of vitamin C attenuated these increases, reducing IL-1β, IL-6, and IFN-γ by 0.63-, 0.56-, and 0.62-fold compared with SiNPs alone. Bone marrow showed decreased cellularity after SiNPs exposure, which vitamin C partially reversed. Caspase-3 expression was upregulated, while Beclin-1 was downregulated following SiNPs exposure, both ameliorated by vitamin C. CONCLUSION: SiNPs induce immune dysfunction through inflammation, apoptosis, and autophagy inhibition. Vitamin C administration significantly counteracts these effects.