Integrative Omics-identified Potential Toxicity of Environmental and Nutritional Metals

Abstract

Introduction Multiple metal ions are present in the human diet, with some being required as essential nutrients and all causing toxicity at high intakes. Low level environmental cadmium (Cd) occurs in human diet and accumulates in vivo. Selenium (Se) is an essential micronutrient, and a component of 25 selenoproteins responsible for physiological functions. However, excess Se increases the risk of diseases, therefore, determination of adequate Se amount for human health is critical. Impacts of metals and their interaction on cells and organs need to be addressed. Methods C57BL6 mice were treated with Se (4 mg Na2SeO4/L, 16 weeks), Cd (3.3 mg CdCl2/L, 16 weeks) and mixture. Metals, redox states, metabolites and phenotypic markers for lung and liver functions were analyzed. Results Urinary Se was 4-6 folds higher in Se-treated group while no changes were observed in lung and liver. Cd levels were elevated in urine, lung and liver in Cd mice. Se-treated mice significant increased body mass than control or Cd groups. Cd oxidized Prx3 in lung but not in liver, and co-treatment showed that Se inhibited Prx3 oxidation. Liver metabolomics of Se-treated mice showed that altered metabolome was significantly associated with weight gain, and accompanied by decreased levels of bile acids and acyl carnitines. Discussion Excess Se disrupts lipids homeostasis. Our study showed that mice treated with Se caused higher Cd accumulation in lung and liver, suggesting that excess Se could elevate Cd toxicity. The results suggest that presence of multiple metal ions in diet could affect human health potentiating metal toxicity.