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 parenteral Zn on Cu metabolism and its relationship to MT in t he intestinal epithelium, liver and kidney. Six-week-old male rats wer e fed for one week a control dict containing 42 mg Zn and 6 mg Cu/kg. They were then divided into three groups. One group continued to recei ve the control diet while another received a similar dict containing 5 60 mg Zn/kg. A third group, fed the control diet, received a subcutane ous dose of 90 mg Zn/kg body weight every 2-3 days for the duration of the experiment. Rats from each group were killed on days 7 and 14. Lo w Cu status in Zn-treated rats was indicated by lower than normal seru m Cu concentration, serum ceruloplasmin activity, low liver and kidney Cu concentrations and low cytochrome C oxidase activity. None of thes e changes, however, were related to an increase in Cu as a result of Z n-induced MT in the intestinal epithelial cell. Instead, as the MT con centrations rose, Cu concentration decreased. This study suggests that the effects of high Zn treatment on Cu status are not the result of t he long-held theory that Zn-induced intestinal MT sequesters Cu and pr events its passage to the circulation. Instead, it may be caused by a direct effect of high lumenal Zn concentrations on Cu transport into t he epithelial cell.