Involvement of intestinal calcium transporter 1 and metallothionein in cadmium accumulation in the liver and kidney of mice fed a low-calcium diet

Essential metals can affect the metabolism of nonessential metals. Calcium (Ca) is an essential mineral that is commonly lacking in the diet. When we fed 5-week-old male mice for 4 weeks on a purified diet containing 0.005% Ca (CaDF mice), the Ca concentration in the plasma, liver and kidneys did not decreased. Cd accumulation increased in the liver and kidneys of CaDF mice given 1 mg/kg Cd orally each day for 5 days, but not in those given intraperitoneal injections of Cd or Cd-metallothionein (Cd-MT). The zinc (Zn) concentration increased significantly in the intestinal cytosol and plasma during the time the mice were fed the low-Ca diet, and expression of both MT-1 and ZnT-1 sharply increased with a similar time course. Intestinal mRNA expression of CaT1, a Ca transporter, was more than 10 times higher in CaDF mice than in controls, although expression of other transporters, including DMT1, decreased in CaDF mice. These results suggest that CaT1 may stimulate the intestinal absorption of Cd and Zn, and some Cd may be distributed to the kidneys along with MT induced by Zn.