Metabolic effects of paraben exposure in geriatric serum: non-targeted metabolomics profiling and association analysis of perturbed metabolic pathways

BACKGROUND: Parabens exist extensively in various pharmaceutical and personal care products (PPCPs). Certain associations have been reported among metabolic diseases and paraben exposure. Metabolomics can be used to explore disease mechanisms via associated biomarker screening. OBJECTIVES: To measure the paraben level in the serum of the elderly and evaluate association between endogenous metabolites and paraben exposure. METHODS: Detection and quantification of four parabens were performed in serum samples. A non-target metabolomic screening and an integrated metabolite annotation were applied to comprehensively analyze the metabolic profiles. Mechanistic analysis of the key enzymes in the enriched pathways was conducted by investigating the molecular docking patterns with paraben ligands. RESULTS: Four parabens were detected with the detection rate over 50 %, among which methyl paraben (MeP) and propyl paraben (PrP) showed the higher detection frequency. The median concentration of MeP was the highest at 3.4 ng/mL. MeP and PrP were also found to have more extensive metabolic association patterns. The pathways related to biosynthesis and metabolism of steroid and fatty acid were enriched as metabolic effects that are widely associated with paraben exposure. The docking modes and interaction characteristics provided explanation from molecular level for the metabolic association analysis. CONCLUSION: Parabens exhibited potential for metabolic disruption, with variation among different structures. Future studies are required to confirm the causal relationships.