Topical Area: Vitamins and Minerals
Multiple metals are present in the human diet, with some being required as essential inorganic nutrients and all causing toxicity in excess or deficiency. Cadmium (Cd), a toxic heavy metal accumulates in human organs, kidney, liver and lung via food consumption. Our recent mouse studies showed that Cd decreased lung selenium level, and caused metabolic and transcriptomic disruption. However, little is known about the effects of Cd on nutritional metal distribution and subsequent impact on human health. In this study, we examined effects of oral Cd on distribution and interaction of nutritional metals in mouse lung.
C57BL/6J mice were treated with Cd at low concentrations (0, 1, 3.3, 10 mg CdCl2/L) by drinking water for 16 weeks. Lungs were collected from mice and lung samples and isolated lung mitochondria were analyzed for 25 inorganic nutritional and toxic environmental metals by inductively coupled plasma mass spectrometry (ICP-MS). In addition, human lung samples from the Emory Transplant Program (Emory IRB 00006248) and from International Institute for Advancement of Medicine were analyzed for metals by ICP-MS.
Results : Lungs (n = 50) from mice exposed to Cd in a dose-response study showed that cobalt (Co), vanadium (V), copper (Cu) and molybdenum (Mo) were positively correlated with Cd [Spearman correlation (r); 0.38, 0.31, 0.42, 0.41, P< 0.05], and correlation of V and Cu to Cd were increased in lung mitochondria (r; 0.73, 0.87). The data for human lungs (n = 24) showed that Cd was positively correlated with Co, V and manganese (Mn), r; 0.43, 0.73 and 0.39, P< 0.05) in chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, emphysema, cystic fibrosis, and negatively correlated with magnesium (r= -0.46).
Conclusions : The results show that Co and V each had positive correlations with Cd in human and mouse lung studies, and interactions of metals with Cd were increased in lung mitochondria. Additionally, the results suggest interactions of Cd with Cu, Mo and Mn, which could impact the function of these essential nutrients. Given the range of toxic effects of Cd, the results indicate that studies are needed to understand potential dysfunctions related to disturbed homeostasis of nutritionally essential metals.
Funding Sources :
NIEHS R01 ES023485 and NIEHS R21 ES025632