title: Treatment with D-penicillamine or zinc sulphate affects copper metabolism and improves but not normalizes antioxidant capacity parameters in Wilson disease.
abstract: Copper accumulation in tissues due to a biallelic pathogenic mutation of the gene: ATP7B results in a clinical phenotype known as Wilson disease (WD). Aberrations in copper homeostasis can create favourable conditions for superoxide-yielding redox cycling and oxidative tissue damage. Drugs used in WD treatment aim to remove accumulated copper and normalise the free copper concentration in the blood. In the current study the effect of decoppering treatment on copper metabolism and systemic antioxidant capacity parameters was analyzed. Treatment naïve WD patients (TNWD) (n = 33), those treated with anti-copper drugs (TWD) (n = 99), and healthy controls (n = 99) were studied. Both TNWD and TWD patients characterised with decreased copper metabolism parameters, as well as decreased total antioxidant potential (AOP), glutathione (GSH) level, activity of catalase, glutathione peroxidase (GPx), and S-transferase glutathione, compared to controls. TWD patients had significantly lower copper metabolism parameters, higher total AOP and higher levels of GSH than TWD individuals; however, no difference was observed between these two patient groups with respect to the rest of the antioxidant capacity parameters. Patients who had undergone treatment with D-penicillamine or zinc sulphate did not differ with respect to copper metabolism or antioxidant capacity parameters, with the exception of GPx that was lower in D-penicillamine treated individuals. These data suggest that anti-copper treatment affects copper metabolism as well as improves, but does not normalize, natural antioxidant capacity in patients with WD. We propose to undertake studies aimed to evaluate the usefulness of antioxidants as well as selenium as a supplemental therapy in WD.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Gromadzka
authors.affiliation: Second Department of Neurology, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957, Warsaw, Poland, gromadz@ipin.edu.pl.
authors.forename: Gromadzka
authors.initials: G
authors.lastname: Grażyna
authors.forename: Agata
authors.initials: A
authors.lastname: Karpińska
authors.forename: Karpińska
authors.initials: K
authors.lastname: Agata
authors.forename: Adam
authors.initials: A
authors.lastname: Przybyłkowski
authors.forename: Przybyłkowski
authors.initials: P
authors.lastname: Adam
authors.forename: Tomasz
authors.initials: T
authors.lastname: Litwin
authors.forename: Litwin
authors.initials: L
authors.lastname: Tomasz
authors.forename: Agata
authors.initials: A
authors.lastname: Wierzchowska-Ciok
authors.forename: Wierzchowska-Ciok
authors.initials: WC
authors.lastname: Agata
authors.forename: Karolina
authors.initials: K
authors.lastname: Dzieżyc
authors.forename: Dzieżyc
authors.initials: D
authors.lastname: Karolina
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Chabik
authors.forename: Chabik
authors.initials: C
authors.lastname: Grzegorz
authors.forename: Anna
authors.initials: A
authors.lastname: Członkowska
authors.forename: Członkowska
authors.initials: C
authors.lastname: Anna
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D005260:Female; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D010396:Penicillamine / Q000494:pharmacology* / Q000627:therapeutic use; D019287:Zinc Sulfate / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D019287:Zinc Sulfate; D003300:Copper; D010396:Penicillamine