Metabolomics reveals that phosphatidylethanolamine can alleviate the toxicity of silica nanoparticles in human lung A549 cells.

Silica nanoparticles (SiNPs) are widely utilized in occupational settings where they can cause lung damage through inhalation. The objective of this research was to explore the metabolic markers of SiNPs-induced toxicity on A549 cells by metabolomics and provide a foundation for studying nanoparticle-induced lung toxicity. Metabolomics analysis was employed to analyze the metabolites of SiNPs-treated A549 cells. LASSO regression was applied for selection, and protective measure experiments were conducted to validate the efficacy of selected potential toxicity mitigators. After SiNPs treatment, 23 differential metabolites were identified, including lipids, nucleotides, and organic oxidants. Pathway analysis revealed involvement in various biological processes. LASSO regression further identified six metabolites significantly associated with SiNPs toxicity. Notably, phosphatidylethanolamine (PE (14:1(9Z)/14:0)) showed enrichment in six significant metabolic pathways and with an AUC of 1 in the ROC curve. Protective measure experiments verified its protective effect on A549 cells and demonstrated its considerable inhibition of SiNPs-induced cytotoxicity. This study elucidated SiNPs-induced cytotoxicity on A549 cells and identified PE as a potential toxicity mitigator. These findings contribute to understanding the mechanisms of nanoparticle-induced lung toxicity and inform occupational health preventive strategies.