Significance of Oxidative Damage to Proteins and DNA in the Blood of Patients with Parkinson's Disease in Assessing the Severity of the Disease

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-hydroxy2-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.