Long-term environmental cadmium exposure induced serum metabolic changes related to renal and liver dysfunctions in a female cohort from Southwest China

Cadmium (Cd), a toxic heavy mental, has been reported to be correlated with increased incidences of multiple diseases. Only a few studies have paid attention to screen the urine metabolites related to long-term environmental Cd exposure in humans. Research on the Cd exposure-related serum metabolic alternations and biological mechanisms linking Cd exposure to adverse health risks in humans is scanty. In this study, we investigated the serum Cd exposure-related metabolic alternations in a cohort of 101 non-smoking females (two polluted groups and one control group) and 18 Cd exposure-related metabolites were identified. A total of 16 clinical indicators of renal and hepatic functions and bone health were measured. Five health effect biomarkers including serum creatinine, alkaline phosphatase, total bilirubin, direct bilirubin and albumin to globulin ratio that are related to impaired renal and hepatic functions showed significant differences among the three groups and had close correlations with Cd levels. We identified intermediate metabolites that were associated with both Cd exposure and health effect biomarkers using a “meet-in-the-middle” approach. Fourteen Cd exposure-related metabolites in the metabolism of glycerophospholipids, sphingolipids, arachidic acid, linoleic acid and amino acids, were identified to be the intermediates of Cd exposure and the health effect biomarkers. Our findings provided evidence for the linkage of long-term environmental Cd exposure and the renal and hepatic insufficiency.