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Adverse health effects caused by exposure to lead (Pb), cadmium (Cd), and arsenic (As) in the environment are of global concerns. Among pathways, incidental ingestion of co-contaminated indoor dust is an important source for child exposure to Pb, Cd, and As. In light of the contribution of indoor dust as an exposure source, it is important to reduce Pb, Cd, and As exposure via indoor dust ingestion. Reducing metal(loid) oral bioavailability via elevating dietary mineral intake may provide a way to simultaneously lower human exposure to co-existing metal(loid)s. The sharing of Pb/Cd with calcium (Ca) transporters provides a chance to manipulate dietary Ca intake to reduce Pb/Cd oral bioavailability. However, the underlying molecular mechanisms have yet to be understood. Unknowns also remain regarding the efficacy of different Ca supplements including inorganic (CaCO3 and CaHPO4) and organic Ca (Ca gluconate, Ca lactate, Ca aspartate, and Ca citrate, which is important for practical use to reduce human metal(loid) exposure. While organic Ca may be more effective in stimulating Ca transporter downregulation, organic ligands may complex with metal(loid)s to increase their solubility in the intestine. In comparison, CaHPO4 may play dual roles in reducing Pb oral bioavailability, with supplied Ca reducing intestinal Ca transporters and phosphate precipitating with Pb to produce sparingly soluble Pb-phosphate precipitates particularly chloropyromorphite [Pb5(PO4)3Cl]. Regarding As oral bioavailability, effects of Ca intake are yet to be explored. Unlike Pb/Cd, AsV is absorbed in the small intestine via phosphate (P) transporters such as the type IIb sodium-phosphate (NaPi-IIb) cotransporters in the apical membrane of enterocytes. Adaption to high levels of dietary Ca may decrease the expression of intestinal Ca transporters to avoid hypercalcemia and maintain Ca homeostasis via decrease in renal synthesis of 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], which critically controls the intestinal expression of both P and Ca transporters. Ca-inhibited renal 1,25(OH)2D3 synthesis may lead to reduced duodenal expression of P transporters, thereby reducing As bioavailability, which remains to be assessed.
Based on in vivo mouse bioassays, this study evaluated the performance and mechanisms of Ca minerals in reducing Pb, Cd, and As oral bioavailability in indoor dust, to identify the most effective Ca minerals. Results showed that In general, mice exposed to each of the Ca minerals exhibited lower Pb-, Cd-, and As-RBA for 3 dusts (Figure 1). However, RBAs with the different Ca minerals varied. Among minerals, mice fed dietary CaHPO4 did not exhibit lower duodenal mRNA expression of Ca transporters, but did have the lowest Pb and Cd oral bioavailability at the highest Ca concentration (5000 g Ca g–1; 5195% and 5274% lower compared to the control). Lead phosphate precipitates (e.g., chloropyromorphite) were observed in feces of mice fed dietary CaHPO4 (Figure 2). In comparison, mice fed organic Ca minerals (Ca gluconate, Ca lactate, Ca aspartate, and Ca citrate) had lower duodenal mRNA expression of Ca transporters, but Pb and Cd oral bioavailability was higher than in mice fed CaHPO4. In terms of As, mice fed Ca aspartate exhibited the lowest As oral bioavailability at the highest Ca concentration (5000 g Ca g–1; 4172% lower) and the lowest duodenal expression of P transporter (88% lower) (Figure 2). The presence of aspartate did not elevate As solubility in the intestine.
Figure 1. Effects of calcium (Ca) minerals on the bioavailability of Pb, Cd, and As contained in orally ingested indoor dusts in mice.
Figure 2. Proposed working model for the regulation of different Ca minerals in oral Pb, Cd, and As bioavailability.
This study elucidates the mechanisms and efficiency of different Ca minerals in reducing exposure to Pb, Cd, and As, being critical to the practical application of optimal Ca minerals to protect humans from Pb, Cd, and As co-exposure in the environment.
This study was published on December 21, 2022 in Environmental Health Perspectives with the title "a Minerals and Oral Bioavailability of Pb, Cd, and As from Indoor Dust in Mice: Mechanisms and Health Implications" (link: //ehp.niehs.nih.gov/doi/10.1289/EHP11730). Assoc. Prof. Hong-Bo Li was the first and corresponding author, while Ph.D student Rong-Yue Xue was the second author of the paper.
This work was supported by the National Natural Science Foundation of China (42022058, 41877356), the National Key Basic Research Program of China (2018YFC1801004), Fundamental Research Funds for the Central Universities (0211/14380155).
