Hyo Min Lee (Kyungpook National University)

윤영란 (Kyungpook National University)

윤영란 (Kyungpook National University)

Ji Seo Park (Kyungpook National University)

Hyo Min Lee (Kyungpook National University)

Mi-Ri Gwon (Kyungpook National University)

Hae Won Lee (Kyungpook National University)

Duk-Hee Lee (Kyungpook National University)

Sook Jin Seong (Kyungpook National University)

Vitamin D (VD) has various positive effects on the body, including the activation of the immune system and the antioxidant pathway. Heavy metals (HMs) that are known to disrupt VD metabolism can limit VD function. VD has also been reported to stimulate HMs absorption. No studies have investigated the impact of HMs on VD activity from a metabolomics perspective, despite the fact that there are a variety of opinions on how exposure to HMs affects VD activity. Therefore, in this study, we identified the endogenous metabolites altered by the effect of HMs exposure on VD activity and investigated their networks.

Using ultra-high performance liquid chromatography and quadrupole time-of-flight/mass spectrometry, 46 plasma samples were analyzed. Untargeted metabolic profiling was performed using two groups: one with relative severe VD deficiency and low level of HMs (lead, cadmium, mercury, and arsenic) (SVDD-low HM), and the other with VD deficiency and high level of HMs (VDD-high HM).

Six metabolites were putatively identified: docosahexaenoic acid (DHA), phosphocholine (PC) 20:5_18:3, diacylglycerol (DAG) 15:0_18:3, PC 18:2_18:3, bilirubin, and eicosapentaenoic acid (EPA). Five metabolites were increased in VDD-high HM compared to SVDD-low HM, and only DAG 15:0_18:3 was decreased. The bilirubin, EPA, and DHA, known as antioxidants, are increased by the antioxidant pathway of VD, which is further activated as a defense mechanism against increased oxidative stress caused by HMs. Also, increased EPA and DHA promote the synthesis of DAG and PCs. In receiver operating characteristic curve analysis, DHA was exhibited an area under the curve of 0.850 with an accuracy of 77.3%. This suggested that DHA is the most suitable for predicting VD activity by HMs exposure.