Regional distribution and localization of zinc and metallothionein in the intestine of rats fed diets differing in zinc content

Background: Zinc (Zn) is protective and enhances epithelial repair in gut d iseases. In this study we investigate the localization and distribution of Zn and its binding protein, metallothionein (MT), in the gut of rats fed di ets varying in Zn content. Methods: Male-Sprague Dawley rats were fed low, normal, high, or excess Zn in their diets (10, 100, 400, or 1000 mg Zn/kg, respectively) and killed 7 days later. Blood, liver, and gut tissues were c ollected. Tissue Zn was determined with atomic absorption spectro-photomete ry and MT with a Cd/haem affinity assay. Zn and MT were immunohistochemical ly localized in the small-intestinal wall with zinquin and an anti-MT antib ody. Results: Most Zn in the intestinal wall was present in the mucosal scr apings, with 94% membrane-bound and 6% cytosolic, irrespective of dietary Z n. MT levels increased in all gut regions at dietary Zn levels above 100 mg Zn/kg. MT was 40% higher in the ileum than in other gut regions in rats fe d low- and normal-Zn diets. The Zn content of the ileum was also 20% higher than that of other gut regions in rats fed low-, normal-, or high-Zn diets . Zn and MT were colocalized in the base of the intestinal crypts, most vis ibly in the ileum. Conclusion: Mucosal cytosolic Zn and MT concentrations a re increased only at high or excessive Zn intakes in all gut regions except the ileum, which can respond to a lower Zn intake. As the cytosolic Zn poo l most likely influences mucosal protection and repair mechanisms, it is pr oposed that an increased MT may indicate the adequacy of oral Zn therapy in gut disease.