|Newman Jr, Samuel|
Submitted to: Journal of Trace Elements in Experimental Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 20, 1996
Publication Date: N/A
Interpretive Summary: There is a genetic disease in humans called Wilson's Disease that causes copper to accumulate in the tissues. A way of treating this disease is to give the patient a lot of dietary zinc. Zinc competes with copper for absorption and prevents too much copper getting into the body. This is a very effective treatment, but not much is known about the potential side effects. We noticed in our animal studies that when a rat was fed a high zinc diet, the intestines seemed to be structurally weak. We decided to use the electron microscopy to determine if there were any visual effects of high zinc feeding on the collagen part of the intestine. Collagen is the material that holds the different parts of the tissue together. We saw that collagen molecules in the intestine of rats fed high zinc was often disorganized and formed tangled masses, whereas in those rats fed a normal amount of zinc, the collagen appeared normal. This suggests that perhaps humans who are fed high zinc for a long time also might show similar problems.
Technical Abstract: The feeding of high zinc diets to humans is often used as therapy for patients with Wilson's disease, an autosomal recessive disorder of copper accumulation. There seems to be no outward adverse effects of this treatment; however, preliminary studies in our laboratory have shown apparent weaknesses in the intestinal wall of rats fed high zinc diets. As sa consequence, this study was carried out to determine if feeding high zinc diets to rats would affect the ultrastructural morphology of the small intestine. The effects of treatment on copper status of the rats also were determined. Weanling male rats were fed diets containing either 35 or 350 mg of zinc/kg. After 7 weeks, blood and various tissues were collected to measure copper status indicators, and portions of the upper duodenum were excised and prepared for light and electron microscopy. Results showed that rats fed high zinc had significantly lower copper status as indicated by low serum copper, serum ceruloplasmin activity, and liver copper, than rats fed normal zinc diets. Liver superoxide dismutase or cytochrome c oxidase activity were not affected by high zinc. Observations of sections of the duodenum by electron microscopy showed that non-assembled collagen molecules of the lamina propria were more often disorganized and formed tangled masses in rats fed the high zinc diet than in those fed normal zinc diets. This suggests that low copper status caused by high zinc feeding might be affecting the activity of lysyl oxidase, a copper-dependent enzyme, and thus cross linking of the collagen molecules. However, these observations did not always correlate with low copper status. Another possible explanation is a direct competition between zinc and copper for sites on lysyl oxidase.