Zinc-and/or cadmium-induced intestinal metallothionein and copper metabolism in adult rats☆

Abstract Feeding diets with high zinc or cadmium concentrations to animals compromises their copper status. Previous work suggested that metallothionein (MT), induced in the intestinal mucosa by zinc or cadmium, binds copper and inhibits its absorption. More recent studies showed that this mechanism may not be operative for zinc and that intestinal MT adapts to long-term feeding of high-zinc diets. The present study was designed to determine the effects of feeding high-zinc and/or high-cadmium diets on the induction of intestinal MT and its subsequent effect on copper status. Six-week-old male rats were placed in a 2 × 2 × 3 factorial experiment with two concentrations of dietary zinc (60 and 350 mg/kg), two concentrations of dietary copper (3 and 9 mg/kg), and three concentrations of dietary cadmium (0, 1, and 5 mg/kg). After 3 weeks, the difference in the MT concentration between rats fed high- and normal-zinc diets was only 1.5 times. However, rats fed the highest amount of cadmium had MT concentrations about five time higher than those not fed cadmium. In both the zinc and cadmium groups, the concentration of intestinal zinc and cadmium followed that of MT; however, the copper concentrations were not changed. Although intestinal MT was not elevated appreciably in zinc-fed rats, the copper status of these rats fed 3 mg of copper/kg of diet was severely depressed. Rats fed 9 mg of copper/kg of diet were not affected. The copper status in rats fed high-cadmium and 3 mg of copper/kg of diet was depressed even more than with a high-zinc diet. This study suggests that the effects of high dietary zinc or cadmium on copper status are not the result of induced intestinal MT binding of copper thus preventing its passage into the circulation.