Stojsavljević Aleksandar, Kozlica Katarina, Šarac Ivana, Lazic Una, Vitković Jelena, Radišić Vanja, Polović Natalija, Svetel Marina, Ščančar Janez
Innovation Center, Faculty of Chemistry, University of Belgrade, Belgrade, Serbia.
Department of Environmental Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
J Pharm Biomed Anal. 2025 Nov 15;265:117029. doi: 10.1016/j.jpba.2025.117029. Epub 2025 Jun 13.
Wilson's disease (WD) is a rare genetic disorder characterized by impaired Cu metabolism in the body. This study aimed to compare the total levels of essential trace elements (Cr, Mn, Fe, Co, Cu, Zn, Se, and Mo) in plasma and urine samples of WD-treated patients (cases) and healthy controls, and to conduct Cu speciation in plasma samples. Inductively coupled plasma mass spectrometry (ICP-MS) was used for total element concentration, while high-performance liquid chromatography (HPLC) coupled to ICP-MS (HPLC-ICP-MS) was used to determine the following Cu species: Cu-ceruloplasmin (Cu-Cp), Cu-human serum albumin (Cu-HSA), and Cu-low molecular mass (Cu-LMM). In plasma, cases had significantly lower levels of Cu, but higher levels of Zn and Se than controls. In urine, cases had significantly higher levels of Cu and Zn, while the levels of Se, Co, and Mo were significantly lower than in controls. Therapy with ZnSO led to higher plasma Zn and Se levels, and higher urine Zn levels, while chelating agent therapy increased urine Cu levels. Among the three Cu species in both cases and controls, the proportion of Cu-Cp was the most dominant, followed by Cu-HSA and Cu-LMM. Long-term drug therapy led to a decline or loss of Cu-HSA and Cu-LMM fractions, offering opportunities for potential plasma biomarkers of WD. Overall, this study provides new insight into the levels of essential trace elements in the plasma and urine of WD-treated cases, the impact of drug therapy on the alteration of specific trace elements and three major species of Cu, potential new biomarkers, and the implications for careful monitoring of drug therapy in WD patients.
威尔逊病（WD）是一种罕见的遗传性疾病，其特征是体内铜代谢受损。本研究旨在比较WD治疗患者（病例组）和健康对照者血浆和尿液样本中必需微量元素（铬、锰、铁、钴、铜、锌、硒和钼）的总水平，并对血浆样本进行铜形态分析。电感耦合等离子体质谱法（ICP-MS）用于测定元素总浓度，而高效液相色谱法（HPLC）与ICP-MS联用（HPLC-ICP-MS）用于测定以下铜形态：铜蓝蛋白结合铜（Cu-Cp）、人血清白蛋白结合铜（Cu-HSA）和低分子量铜（Cu-LMM）。在血浆中，病例组的铜水平显著低于对照组，但锌和硒水平高于对照组。在尿液中，病例组的铜和锌水平显著高于对照组，而硒、钴和钼水平显著低于对照组。硫酸锌治疗导致血浆锌和硒水平升高，尿液锌水平升高，而螯合剂治疗则增加尿液铜水平。在病例组和对照组的三种铜形态中，Cu-Cp的比例最为占主导地位，其次是Cu-HSA和Cu-LMM。长期药物治疗导致Cu-HSA和Cu-LMM组分减少或消失，为WD潜在的血浆生物标志物提供了机会。总体而言，本研究为WD治疗病例的血浆和尿液中必需微量元素水平、药物治疗对特定微量元素和三种主要铜形态变化的影响、潜在的新生物标志物以及对WD患者药物治疗进行仔细监测的意义提供了新的见解。
