Zinc therapy increases duodenal concentrations of metallothionein and ironin Wilson's disease patients

Objective: Wilson's disease is effectively treated by zinc administration w hich, in vitro, increases metallothionein concentrations. To ascertain whet her the latter also occurs in humans we measured metallothionein and trace element concentrations in the duodenal mucosa of 15 Wilson's disease patien ts: 12 treated with zinc sulphate, two treated with penicillamine, and one not yet on treatment. The control group consisted of 17 patients with dyspe psia, who underwent the same study protocol. Methods: Metallothionein and t race element concentrations were measured in duodenal mucosa biopsies accor ding to the silver-saturation hemolysate method and atomic absorption spect rophotometry. Results: Metallothionein concentrations increased by 1500% af ter zinc and 150% after penicillamine in Wilson's disease patients, with re spect to controls who had negative endoscopy and Wilson's disease patients who were not treated. A significant correlation was found between metalloth ionein and duodenal zinc concentrations. Mucosal iron concentration increas ed in Wilson's disease patients whether they were treated with zinc or peni cillamine, Duodenum with duodenitis also had significantly increased iron l evels compared with normal duodenum, Conclusions: Zinc administration incre ases intestinal metallothionein in Wilson's disease patients. The blockade of copper absorption and its elimination in the stools on desquamation of t he intestinal cells probably explains one of the mechanisms underlying the effect of zinc treatment, Despite normal endoscopy, Wilson's disease patien ts present increased mucosal iron concentrations similar to those in contro ls with duodenitis. Metallothionein may therefore prevent oxidative damage caused by metal toxicity. (Am J Gastroenterol 1999;94:334-338, (C) 1999 by Am. Cell, of Gastroenterology).