The state of systemic oxidative stress during Parkinson’s disease

Abstract

The development of oxidative stress is considered as one of the key molecular mechanisms that lead to the death of dopamine-producing neurons in Parkinson’s disease (PD). Here, we characterized the oxidative status (OS) of patients depending on the severity of the disease, the time course of the disease, and treatment with antiparkinsonian drugs. The OS was evaluated using Fe2+-induced chemiluminescence of serum lipoproteins (LPs) on the basis of informative parameters, including preformed lipid hydroperoxides, the maximum intensity of lipid peroxidation (LPO) and LP resistance to oxidation, due to the activity of the endogenous antioxidant system. In all patients, regardless of the disease stage (second, third, or fourth), we observed a comparable unidirectional increase in the level of lipid hydroperoxides and maximum intensity of (LPO). However, the activity of the endogenous antioxidant system decreased proportionally to the disease severity: second stage > third stage > fourth stage. In patients at the second and third stages of the disease who were treated with antiparkinsonian drugs we found a disruption of the OS in comparison with untreated patients of the same stage. In general, the deterioration of the OS in patients at the second and third stages of the disease, which included an increase in the level of lipid hydroperoxides and the maximum intensity of LPO, was detected in both patients receiving levodopa at a daily dose of more than 300 mg and in patients treated with drugs that did not contain levodopa. The decrease in the activity of the endogenous antioxidant system in these patients did not depend on the method of treatment and the dose of levodopa. The duration of treatment (up to 5 years) did not influence the OS of patients at the second and third stages of the disease. These data confirm the concept of the significance of oxidative stress in the pathogenesis of PD and indicate the advisability of using antioxidant drugs in complex therapy of PD.