ZINC-INDUCED METALLOTHIONEIN AND COPPER-METABOLISM IN INTESTINAL-MUCOSA, LIVER, AND KIDNEY OF RATS

Large doses of parenteral zinc (Zn) and/or the feeding of high Zn diet s to animals or humans for long periods affects copper (Cu) metabolism . Previous work suggests that Zn-induced metallothionein (MT) in intes tinal epithelial cells binds Cu and inhibits its absorption. This stud y was designed to determine the effects of treating rats with high die tary or high parenteral Zn on Cu metabolism and its relationship to MT in the intestinal epithelium, liver and kidney. Six-week-old male rat s were fed for one week a control diet containing 42 mg Zn and 6 mg Cu /kg. They were then divided into three groups. One group continued to receive the control diet while another received a similar diet contain ing 560 mg Zn/kg, A third group, fed the control diet, received a subc utaneous dose of 90 mg Zn/kg body weight every 2-3 days for the durati on of the experiment. Rats from each group were killed on days 7 and 1 4. Low Cu status in Zn-treated rats was indicated by lower than normal serum Cu concentration, serum ceruloplasmin activity, low liver and k idney eu concentrations and low cytochrome C oxidase activity. None of these changes, however, were related to an increase in Cu as a result of Zn-induced MT in the intestinal epithelial cell. Instead, as the M T concentrations rose, Cu concentration decreased. This study suggests that the effects of high Zn treatment on Cu status are not the result of the long-held theory that Zn-induced intestinal MT sequesters Cu a nd prevents its passage to the circulation. Instead, it may be caused by a direct effect of high lumenal Zn concentrations on Cu transport i nto the epithelial cell.