Zinc treatment prevents lipid peroxidation and increases glutathione availability in Wilson's disease

Abstract

Oxidative and reductive mechanisms are important in Wilson's disease. In this study, we sought to evaluate tissue levels of glutathione and cysteine, an important detoxification system, and of malondialdehyde, a marker of lipoperoxidation, in patients with Wilson's disease receiving penicillamine or zinc treatment, in comparison with patients with chronic liver disease of different origin. Concentrations of cysteine, reduced/oxidized glutathione, malondialdehyde, zinc, and copper were determined (with the use of high-pressure liquid chromatography, fluorimetry and atomic-absorption spectrophotometry) in liver-biopsy specimens from 24 patients with Wilson's disease (18 treated with zinc, 6 with penicillamine), 34 patients with chronic viral hepatitis, and 10 patients with alcoholic liver disease. In patients with Wilson's disease, the concentration of reduced glutathione was lower than that in patients with viral hepatitis and as high as that in subjects with alcoholic liver damage. The cysteine level was significantly lower than those in the control groups, and the percentage of oxidized glutathione/total glutathione was higher than that in viral or alcoholic disease. Malondialdehyde levels were low, but when zinc- and penicillamine-treated patients were considered separately, only the former had low malondialdehyde levels. Zinc-treated patients had higher concentrations of reduced glutathione and a lower percentage of oxidized glutathione. In summary, patients with Wilson's disease have relevant glutathione depression, with low levels of reduced glutathione and cysteine and high concentrations of oxidized glutathione: This is prevented by zinc administration, which inhibits lipid peroxidation and increases glutathione availability.