Gromadzka Grażyna, Karpińska Agata, Przybyłkowski Adam, Litwin Tomasz, Wierzchowska-Ciok Agata, Dzieżyc Karolina, Chabik Grzegorz, Członkowska Anna
Biometals. 2014 Feb;27(1):207-15. doi: 10.1007/s10534-013-9694-3. Epub 2013 Dec 25.
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.
由于ATP7B基因的双等位基因致病性突变导致组织中铜蓄积，会引发一种名为威尔逊病（WD）的临床表型。铜稳态异常可为产生超氧化物的氧化还原循环和组织氧化损伤创造有利条件。WD治疗中使用的药物旨在清除蓄积的铜并使血液中游离铜浓度正常化。在本研究中，分析了排铜治疗对铜代谢和全身抗氧化能力参数的影响。研究对象包括未经治疗的WD患者（TNWD）（n = 33）、接受抗铜药物治疗的患者（TWD）（n = 99）以及健康对照者（n = 99）。与对照组相比，TNWD和TWD患者的铜代谢参数均降低，总抗氧化潜力（AOP）、谷胱甘肽（GSH）水平、过氧化氢酶、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽S-转移酶的活性也均降低。TWD患者的铜代谢参数显著低于TNWD患者，总AOP和GSH水平则高于TNWD患者；然而，在其余抗氧化能力参数方面，这两组患者之间未观察到差异。接受D-青霉胺或硫酸锌治疗的患者在铜代谢或抗氧化能力参数方面没有差异，但D-青霉胺治疗的个体中GPx较低。这些数据表明，抗铜治疗会影响铜代谢，同时改善WD患者的天然抗氧化能力，但不能使其正常化。我们建议开展研究，以评估抗氧化剂以及硒作为WD补充治疗的有效性。
