Effect of zinc supplementation on metallothionein, copper, and zinc concentration in various tissues of copper-loaded rats.

The present study was designed to investigate the effects of Zn administration on metallothionein concentrations in the liver, kidney, and intestine of copper-loaded rats. Male CD rats were fed a diet containing 12 mg Cu and 67 mg Zn/kg body wt. They were divided into either acute or chronic experimental protocols. Rats undergoing acute experiments received daily ip injections of either Cu (3 mg/kg body wt) or Zn (10 mg/kg body wt) for 3 d. Chronic experiments were carried out on rats receiving Cu ip injections on d 1, 2, 3, 10, 17, and 24, Cu injections plus a Zn-supplemented diet containing 5 g Zn/kg solid diet, or a Zn-supplemented diet alone. Rats injected Zn or Cu had increased MT concentrations in liver and kidney. Zn produced the most important effects and the liver was the most responsive organ. Rats fed a Zn-supplemented diet had significantly higher MT concentrations in liver and intestine with respect to controls. Increased MT synthesis in the liver may contribute to copper detoxification; the hypothesis of copper entrapment in enterocytes cannot be confirmed.

Zinc therapy in Wilson's disease: observations in five patients.

We report our experience with zinc (Zn) therapy in five patients with Wilson's disease (WD). In addition to neurologic examination, evaluation of Kayser-Fleischer rings and liver function tests, copper (Cu) and Zn concentrations in liver tissue, plasma, and urine were periodically evaluated by spectrophotometry. Many of the patients had had side effects due to penicillamine (PCA). Oral Zn sulphate (220 mg tid) reduced the WD symptoms and resulted in normal urinary Cu excretion in all five patients. One patient who had a transient gastric complaint during Zn administration, and in whom a decrease in liver Cu content was not observed, did not show any improvement in liver histology. He resumed PCA therapy after 29 months of Zn therapy. We conclude that long-term Zn treatment in Wilson's disease can be a safe and effective alternative to Cu chelating agents. However, patients should be periodically monitored for their Cu/Zn status to assess patient compliance with therapy.