Are oxidative stress markers useful to predict clinical progression in Parkinson’s disease? A case-control study

Abstract

Objective: To compare the levels of lipid peroxidation products between Parkinson’s disease (PD) and study controls, and the relationship of these products in relation to clinical progression in PD. Background: Oxidative stress may be important in the pathogenesis of Parkinson’s disease (PD). The extent of oxidative stress damage was assessed using markers of lipid peroxidation in a cohort of PD patients and study controls. Methods: A total of 62 PD patients and 86 age-gender matched study controls (25 ischemic stroke and 61 community-based healthy controls) participated in this study. Their demographic and clinical characteristics were obtained using a standardized questionnaire. In PD patients, the clinical severity of their disease was assessed using the Hoehn-Yahr scale and the Unified Parkinson’s Disease Rating scales (UPDRS), and their cumulative exposure to levodopa calculated. Markers of lipid peroxidation (F2-isoprostanes, F2-IsoPs; hydroxyeicosatetraenoic acid, HETEs; and cholesterol oxidation products, COPs), were assessed in the plasma and urine samples using the gas chromatography-mass spectrometry method. Results: The mean (standard deviation) age was 64 (8) years and there were no differences in the gender, ethnicity and medical history in the PD and study control groups (p>0.05). Higher levels of plasma esterified F2-IsoPs, plasma free HETEs and COPs were observed in PD patients as compared to stroke and healthy controls (p<0.05, t-test). No significant correlation was observed between F2- IsoPs, HETEs and COPs in relation to the cumulative dosage of levodopa (r5 -0.15 to 0.21). A significant decrease in plasma free F2-IsoPs was observed with clinical progression of PD, according to the Hoehn-Yahr (p-trend<0.05) and UPDRS severity scales (r5 -0.372, p50.004). After adjusting for age, gender and cumulative levodopa dosage, lower plasma levels of free F2-IsoPs independently predicted UPDRS scores (OR -292, 95% CI -527 to -56). Conclusions: We identified certain markers of lipid peroxidation and COPs to be elevated in PD and suggested the use of plasma free F2-IsoPs as a potential marker of clinical progression.