Identifying Early Urinary Metabolic Changes with Long-Term Environmental Exposure to Cadmium by Mass-Spectrometry-Based Metabolomics

Cadmium (Cd) is a common environmental pollutant, and urinary Cd (UCd) is generally used as a marker of exposure; however, our understanding on the related urinary metabolic changes caused by Cd exposure is still not clear. In this study, we applied a mass-spectrometry-based metabolomic approach to assess the urinary metabolic changes in human with long-term environmental Cd exposure, aimed to identify early biomarkers to assess Cd nephrotoxicity. Urine samples from 94 female never smokers aged 44–70 with UCd in the range of 0.20–68.67 μg/L were analyzed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS) and gas chromatography–mass spectrometry (GC–MS). It was found that metabolites related to amino acid metabolism (l-glutamine, l-cystine, l-tyrosine, <i>N</i>-methyl-l-histidine, l-histidinol, taurine, phenylacetylglutamine, hippurate, and pyroglutamic acid), galactose metabolism (d-galactose and <i>myo</i>-inositol), purine metabolism (xanthine, urea, and deoxyadenosine monophosphate), creatine pathway (creatine and creatinine), and steroid hormone biosynthesis (17-α-hydroxyprogesterone, tetrahydrocortisone, estrone, and corticosterone) were significantly higher among those with a UCd level higher than 5 μg/L. Moreover, we noticed that the level of <i>N</i>-methyl-l-histidine had already started to elevate among individuals with a UCd concentration of ≥2 μg/L. The overall findings illustrate that metabolomics offer a useful approach for revealing metabolic changes as a result of Cd exposure