Investigation of dynamic thiol/disulfide homeostasis and nitrosative stress in patients with wilson disease

INTRODUCTION AND AIM. Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism, resulting in copper accumulation, toxicity in the liver, and eventually in the brain. Oxidative stress may play a role in the pathogenesis of WD, but the roles of dynamic thiol/disulfide homeostasis and nitrosative stress have not been studied. The objective of this study was to assess whether there is a change in thiol/disulfide homeostasis and nitrosative stress in patients with WD. MATERIAL AND METHOD. A total of 50 patients with WD (42 under drug treatment and 8 newly diagnosed patients with no drug treatment) and 50 healthy age- and sex-matched controls included to this study. Serum total thiol and native thiol levels have been measured with a spectrophotometric method. The amount of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide (NO) and 3-nitrotyrosine (3-NT) levels were detected using a chemiluminescence and ELISA assays, respectively. RESULTS. The average native thiol levels of the patient group after drug treatment were found to be significantly higher than those levels of controls (P<0.05). We detected no marked changes in total thiol, disulfide, disulfide/total thiol, disulfide/native thiol, or native thiol/total thiol ratios between groups. We found marked elevations in NO levels in newly diagnosed WD group, and 3-NT levels in newly diagnosed and under drug treatment WD groups when compared to controls (respectively, p<0.05, p<0.01). CONCLUSION. These results are suspected that thiol/disulfide homeostasis and nitrosative stress can play a role in the pathogenesis of WD.