Metabolomic analysis of the inhibitory effect of phthalates and bisphenol A on the antioxidant activity of vitamin D in human samples using liquid chromatography–mass spectrometry

Vitamin D is important because it has roles in maintaining musculoskeletal health, redox homeostasis, and the immune system; however, it is commonly dysregulated by endocrine disrupting chemicals, particularly phthalates and bisphenol A (BPA). Continuous exposure to phthalates and BPA may alter the endogenous metabolite profiles associated with vitamin D activity, although the specific metabolites are yet to be identified. In this study, we identified the endogenous metabolites altered by phthalates and BPA exposure through untargeted metabolic profiling and investigated the role of these metabolites in vitamin D activity. Plasma metabolic profiling using liquid chromatography-mass spectrometry was performed in two groups: severe 25-hydroxyvitamin D (25(OH)D) deficiency and high exposure to phthalates and BPA (Group A) and 25(OH)D deficiency and low exposure to phthalates and BPA (Group B). Multivariate analysis revealed a distinct separation between the two groups. A total of six metabolites were annotated, of which levels of two were significantly different between the two groups: platelet-activating factor (PAF) C16 or lysophosphatidylcholine (lysoPC) 18:0, and 11Z-eicosenamide. Plasma levels of PAF C16 or lysoPC 18:0 were increased in Group A and exhibited an area under the curve of 0.769 with an accuracy of 74.4% in a receiver operating characteristic curve analysis. These metabolites are generated as byproducts of lipid peroxidation, which supports the fact that phthalates and BPA induce oxidative stress in cells. Furthermore, PAF C16 and lysoPC 18:0 may be involved in the network that interferes with the antioxidant activity of vitamin D upon exposure to phthalates and BPA. This study results provide useful information on how the activity of vitamin D on the antioxidant system is inhibited when exposure to phthalates and BPA.