Urinary metabolic alterations associated with occupational exposure to metals and polycyclic aromatic hydrocarbons...

Long-term occupational exposure to metals and organics have been reported to be under great health risks. However, limited data are available on the molecular mechanism between combined exposure to metals and polycyclic aromatic hydrocarbons (PAHs) and harmful health effects. In present work, non-target metabolomics study was conducted based on urine samples from nonferrous metal smelting workers (n = 207), surrounding residents (n = 180), and the control residents (n = 187) by using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Differential and correlation analyses among metabolic features indicate that total 22 differential metabolites in smelting workers were associated (p < 0.05) with metal and PAH exposure. Particularly, amino acid metabolism was strongly disturbed, and other metabolic pathways, including steroid hormone biosynthesis, citrate cycle, and pantothenate and coenzyme A (CoA) biosynthesis were also perturbed. Among them, steroid hormone biosynthesis was more affected by PAH exposure than metals, especially for hydroxyphenanthrene. These altered pathways were closely associated with oxidative stress, inflammation, and energy metabolism disorder. Additionally, our results indicate that endogenous metabolism in surrounding residents were also affected by nonferrous metal smelting activities to some extent. Our work provides valuable insights into molecular mechanisms of adverse health effects probably induced by combined exposure to metals and PAHs.