Toxic effects and mechanisms of methyl 4-hydroxybenzoate in allergic rhinitis: a multi-omics and toxicology study.

PURPOSE: Exogenous chemical exposure is closely associated with allergic rhinitis (AR). Methyl 4-hydroxybenzoate (MeP), a widely used preservative, poses risks of long-term human exposure. This study aimed to explore the potential association between MeP and AR as well as its underlying molecular characteristics. METHODS: Integrating toxicological assessment, bioinformatics analysis, and machine learning approaches, this study identified overlapping targets between MeP and AR using transcriptomic data from AR patients (GSE118243, GSE43523) in the GEO database through multi-platform prediction. Subsequently, key targets were identified through differential expression analysis, functional enrichment, PPI network construction, and three machine learning approaches (Boruta, SVM, and Lasso). Further validation was performed using immune infiltration analysis, GSEA, molecular docking, and qRT-PCR experiments. RESULTS: MeP exhibits moderate lipophilicity, low bioaccumulation potential, and toxic effects on specific organisms. Identify ESR2, IL2, and SLC3A2 as key targets, with significant expression differences (p < 0.05) validated in independent datasets and clinical samples. Immune infiltration analysis suggests MeP may contribute to AR progression by modulating the proportions of B cells, M2 macrophages, neutrophils, and other immune cells. GSEA reveals that key targets are enriched in pathways related to metabolism, inflammation, and autophagy. CONCLUSION: Bioinformatics analyses suggest that MeP is correlated with AR development, and this correlation may involve the modulation of ESR2, IL2, and SLC3A2, as well as influences on immune cell infiltration and related signaling pathways.