Abstract—Oxidative stress (OS) plays an important role in the cascade of events leading to the degeneration of dopaminergic neurons in Parkinson’s disease (PD). Oxidative damage to proteins and nucleic acids contributes to this process. Reactive oxygen and nitrogen species cause protein nitration and the formation of the stable compound 3-nitrotyrosine (3-NT), which characterizes the development of nitrosyl stress, as well as nucleic acids which form the product of DNA oxidation, 8-hydroxy-2-deoxyguanosine (8-OH-dG). Protein and DNA oxidation products are present in the biological fluids of PD patients, however, data on their quantitative content depending on the severity of the disease are contradictory. The aim of this work was to compare the level of products of oxidative damage of proteins and DNA in the blood of patients with PD at different stages. The content of 3-nitrotyrosine (3-NT) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) was measured in the peripheral blood of 134 PD patients at different disease stages (1–4), according to the Hoehn-Yahr functional scale. An increase in the level of 3-NT in blood plasma was observed in all examined patients. In patients at the 2nd, 3rd and 4th stages of the disease, the increase in 3-NT relative to the control was on average 58%, and 30% in patients on the 1st stage, which is significantly different from data obtained at more advanced stages of the disease. Therefore, an increase in the product of oxidative protein metabolism 3-NT in the blood plasma of PD patients is an early PD biomarker, whose expression increases with the progression of the neurodegenerative process. An increase in the level of 8-hydroxy-2-deoxyguanosine relative to the norm was shown in the blood serum of all patients examined. In patients at the 1st, 2nd and 3rd stages of the disease, this increase was on average 60% and, in the most severe cases at the 4th stage of the disease, 183% relative to the control values, which is three times higher than the corresponding values in the other compared subgroups. Thus, the level of 8-hydroxy-2-deoxyguanosine is a biomarker of the most severe disease stages. In this study, we found a systemic increase in the content of both 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine in blood of patients. The data on the increase in the protein and DNA oxidation products in blood of patients at the first stage of the disease, who had not received any treatment, are of particular importance. The identification of biomarkers of oxidative damage of proteins and nucleic acids at the early stages of PD is an important step towards improving the existing diagnostic criteria, as well as identifying individuals at risk. A significant increase in the content of 8-hydroxy-2-deoxyguanosine in the blood serum of patients at the 4th stage of the disease reflects an association between this index and disease severity and may be important for objective evaluation of disease progression. In general, understanding the pathogenetic factors responsible for the death of dopaminergic neurons, including oxidative damage of lipids, proteins, and nucleic acids, may be of great importance for the development of complex neuroprotective approaches to the treatment of PD and assessment of the effectiveness of treatment.

摘要—氧化应激 (OS) 在导致帕金森病 (PD) 多巴胺能神经元退化的级联事件中发挥重要作用。对蛋白质和核酸的氧化损伤促成了这一过程。活性氧和氮物种导致蛋白质硝化和稳定化合物 3-硝基酪氨酸 (3-NT) 的形成，这是亚硝酰应激的发展特征，以及形成 DNA 氧化产物的核酸，8-羟基-2 -脱氧鸟苷 (8-OH-dG)。蛋白质和 DNA 氧化产物存在于 PD 患者的生物体液中，然而，它们的定量数据取决于疾病的严重程度是矛盾的。这项工作的目的是比较不同阶段 PD 患者血液中蛋白质和 DNA 氧化损伤产物的水平。根据 Hoehn 的说法，在 134 名处于不同疾病阶段 (1-4) 的 PD 患者的外周血中测量了 3-硝基酪氨酸 (3-NT) 和 8-羟基-2-脱氧鸟苷 (8-OH-dG) 的含量。 -Yahr 功能量表。在所有接受检查的患者中都观察到血浆中 3-NT 水平的增加。在疾病2、3、4期患者中，3-NT相对于对照组平均增加58%，1期患者增加30%，与更晚期获得的数据有显着差异疾病的阶段。因此，PD患者血浆中氧化蛋白代谢产物3-NT的增加是PD的早期生物标志物，其表达随着神经退行性过程的进展而增加。所有受检患者的血清中均显示 8-羟基-2-脱氧鸟苷水平相对于正常水平有所增加。在疾病的第 1、第 2 和第 3 阶段的患者中，这种增加平均为 60%，在疾病第 4 阶段的最严重病例中，相对于对照值增加了 183%，比对照值高出三倍。其他比较子组中的相应值。因此，8-羟基-2-脱氧鸟苷的水平是最严重疾病阶段的生物标志物。在这项研究中，我们发现患者血液中 3-硝基酪氨酸和 8-羟基-2-脱氧鸟苷的含量系统性增加。未接受任何治疗的疾病第一阶段患者血液中蛋白质和 DNA 氧化产物增加的数据特别重要。在 PD 早期阶段鉴定蛋白质和核酸氧化损伤的生物标志物是改进现有诊断标准以及识别处于危险中的个体的重要一步。疾病 4 期患者血清中 8-羟基-2-脱氧鸟苷含量的显着增加反映了该指数与疾病严重程度之间的关联，可能对客观评估疾病进展很重要。一般来说，了解导致多巴胺能神经元死亡的致病因素，包括脂质、蛋白质和核酸的氧化损伤，对于开发复杂的神经保护方法来治疗 PD 和评估其有效性可能具有重要意义。治疗。