Faculty of Medicine, University of Nis, 18000 Nis, Serbia.
Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia.
Oxid Med Cell Longev. 2020 Aug 18;2020:8209727. doi: 10.1155/2020/8209727. eCollection 2020.
Balkan endemic nephropathy (BEN) represents a chronic tubulointerstitial nephropathy which is followed by the progression of kidney fibrosis to end-stage kidney failure. The critical involvement of poisons in food (aristolochic acid (AA), ochratoxin, and heavy metals) and selenium deficiency are among nutritive factors which contribute to the pathogenesis of BEN, due to reactive oxygen species (ROS) liberation and/or decreased antioxidative defence system. The aim of the study is to distinguish a possible systemic and local origin of ROS through the measurement of xanthine oxidase (XO) activity in urine and plasma, along with the determination of the oxidative changes in lipids and proteins. The study included 50 patients with BEN and 38 control healthy subjects. We noted increased levels of both thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPPs) in the plasma of patients with BEN, compared to the control group ( < 0.001). The urinary levels of AOPPs were higher in patients with BEN in comparison to the control ( < 0.001). The specific activity of XO was significantly lower in plasma and urine in BEN samples, compared to controls ( < 0.005). Based on these results, we hypothesize that XO might not be considered a direct systemic or local contributor to ROS production in BEN, most probably because of the diminished kidney functional tissue mass and/or AA-induced changes in purine nucleotide conformation. The increased AOPP and TBARS level in both plasma and urine in BEN may predict ROS systemic liberation with toxic local effects.
巴尔干地方性肾病（BEN）是一种慢性肾小管间质性肾病，随后肾脏纤维化进展为终末期肾衰竭。食物中毒素（马兜铃酸（AA）、赭曲霉毒素和重金属）和硒缺乏的关键作用以及活性氧物种（ROS）的释放和/或抗氧化防御系统的减少是导致 BEN 发病机制的营养因素之一。本研究的目的是通过测量尿液和血浆中的黄嘌呤氧化酶（XO）活性以及确定脂质和蛋白质的氧化变化，来区分 ROS 的可能全身和局部来源。该研究纳入了 50 名 BEN 患者和 38 名健康对照组。与对照组相比，我们观察到 BEN 患者的血浆中硫代巴比妥酸反应性物质（TBARS）和高级氧化蛋白产物（AOPP）水平升高（<0.001）。与对照组相比，BEN 患者的尿液 AOPP 水平更高（<0.001）。与对照组相比，BEN 样本的血浆和尿液中 XO 的比活性显著降低（<0.005）。基于这些结果，我们假设 XO 可能不能被认为是 BEN 中 ROS 产生的直接全身或局部贡献者，最可能是因为肾脏功能性组织质量减少和/或 AA 诱导的嘌呤核苷酸构象改变。BEN 患者的血浆和尿液中 AOPP 和 TBARS 水平升高可能预示着 ROS 的全身释放及其对局部的毒性作用。
