Lipid Peroxidation Products in the Blood Plasma of Patients with Parkinson’s Disease as Possible Biomarkers of Different Stages of the Disease

Abstract

Abstract—Oxidative stress (OS) plays a significant role in the pathogenesis of Parkinson’s disease (PD) and is accompanied by the development of free radical reactions of lipid peroxidation. The growth of highly reactive products of oxidative metabolism of polyunsaturated fatty acids (PUFAs) leads to dysfunction and the subsequent death of dopaminergic neurons and contributes to the emergence and progression of PD. This paper assesses the prognostic significance of lipid peroxidation (LPO) products determined in the blood of patients with PD as possible biomarkers of various stages of the disease. The content of lipid hydroperoxides (LH), malondialdehyde (MDA), and 4-hydroxynonenals (4-HNE) was determined in the peripheral blood of 240 patients at stages 1–4 of the disease according to the Hoehn and Yahr scale. For all examined patients, regardless of the stage of the disease (stages 2–4), an increase in the level of lipid hydroperoxides by 20% was observed, on average. Elevated levels of MDA were registered in patients with a higher disease severity who were at the advanced stages of the disease (stages 3 and 4). For patients at stages 1 and 2 of the disease the content of MDA remained within normal levels. The content of 4-HNE increased in patients at stages 2, 3, and 4 of the disease proportionally to the severity of the disease. The most pronounced increase in the content of 4-HNE was detected in patients at the advanced stages of the disease (stages 3 and 4). In patients at the second, earlier stage of the disease, the value of this parameter was 34% lower than that in patients at the advanced stages. In patients at the first stage of the disease, all measured parameters of LPO were comparable to control values and therefore could not play a significant diagnostic biomarker role. An important aspect of this study is that some LPO markers (LH and 4-HNE) are associated with both early and late stages of the disease, while the content of MDA increased at the advanced stages. Therefore, MDA and 4-HNE may have a high prognostic value, reflecting the severity of the disease. The most sensitive and specific indicator of LPO is 4-HNE, since its content increases proportionally to the severity of the disease (stage 2 < stage 3 < stage 4). The results we obtained are important for the development of complex neuroprotective approaches to the treatment of this disease, which can prevent the selective death of nervous tissue in PD and delay the development of the neurodegenerative process.