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

Am J Gastroenterol. 1999 Feb;94(2):334-8. doi: 10.1111/j.1572-0241.1999.851_w.x.


Objective: Wilson's disease is effectively treated by zinc administration which, in vitro, increases metallothionein concentrations. To ascertain whether the latter also occurs in humans we measured metallothionein and trace element concentrations in the duodenal mucosa of 15 Wilson's disease patients: 12 treated with zinc sulphate, two treated with penicillamine, and one not yet on treatment. The control group consisted of 17 patients with dyspepsia, who underwent the same study protocol.

Methods: Metallothionein and trace element concentrations were measured in duodenal mucosa biopsies according to the silver-saturation hemolysate method and atomic absorption spectrophotometry.

Results: Metallothionein concentrations increased by 1500% after zinc and 150% after penicillamine in Wilson's disease patients, with respect to controls who had negative endoscopy and Wilson's disease patients who were not treated. A significant correlation was found between metallothionein and duodenal zinc concentrations. Mucosal iron concentration increased in Wilson's disease patients whether they were treated with zinc or penicillamine. Duodenum with duodenitis also had significantly increased iron levels compared with normal duodenum.

Conclusions: Zinc administration increases intestinal metallothionein in Wilson's disease patients. The blockade of copper absorption and its elimination in the stools on desquamation of the intestinal cells probably explains one of the mechanisms underlying the effect of zinc treatment. Despite normal endoscopy, Wilson's disease patients present increased mucosal iron concentrations similar to those in controls with duodenitis. Metallothionein may therefore prevent oxidative damage caused by metal toxicity.

MeSH terms

  • Adult
  • Case-Control Studies
  • Chelating Agents / therapeutic use
  • Copper / metabolism
  • Duodenitis / metabolism
  • Duodenum / metabolism*
  • Female
  • Hepatolenticular Degeneration / drug therapy*
  • Hepatolenticular Degeneration / metabolism
  • Humans
  • Intestinal Mucosa / metabolism
  • Iron / metabolism*
  • Male
  • Metallothionein / metabolism*
  • Penicillamine / therapeutic use
  • Zinc Sulfate / therapeutic use*


  • Chelating Agents
  • Zinc Sulfate
  • Copper
  • Metallothionein
  • Iron
  • Penicillamine