Original Contribution
Oxidative damage in Parkinson disease: Measurement using accurate biomarkers

https://doi.org/10.1016/j.freeradbiomed.2009.11.026Get rights and content

Abstract

Oxidative damage has been implicated in the pathogenesis of Parkinson disease (PD) but the literature data are confusing. Using products of lipid and DNA oxidation measured by accurate methods, we assessed the extent of oxidative damage in PD patients. The levels of plasma F2-isoprostanes (F2-IsoPs), hydroxyeicosatetraenoic acid products (HETEs), cholesterol oxidation products, neuroprostanes (F4-NPs), phospholipase A2 (PLA2) and platelet activating factor–acetylhydrolase (PAF-AH) activities, urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), and serum high-sensitivity C-reactive protein were compared in 61 PD patients and 61 age-matched controls. The levels of plasma F2-IsoPs, HETEs, 7β-and 27-hydroxycholesterol, 7-ketocholesterol, F4-NPs, and urinary 8-OHdG were elevated, whereas the levels of plasma PLA2 and PAF-AH activities were lower, in PD patients compared to controls (p <  0.05). The levels of plasma F2-IsoPs, HETEs, and urinary 8-OHdG were higher in the early stages of PD (p trend <  0.05). There was a significant negative correlation between the cumulative intake of levodopa and urinary 8-OHdG (r =  −0.305, p =  0.023) and plasma total HETEs (r =  −0.285, p =  0.043). Oxidative damage markers are systemically elevated in PD, which may give clues about the relation of oxidative damage to the onset and progression of PD.

Section snippets

Study population

Consecutive patients with PD and community-based age-matched healthy controls were recruited from the outpatient Movement Disorders Clinic after written patient consent and approval from the ethics committee of the National University Hospital, Singapore, were obtained. Clinical information (including age, gender, ethnicity, medical history, weight and height, and smoking status) was collected using standardized questionnaires. PD patients were diagnosed according to the UK Parkinson Disease

Clinical characteristics

Sixty-one cases and 61 controls were included in this study. Comparison between the demographic characteristics (such as age, gender, race, and body mass index) and medical histories of the study population did not reveal significant differences between cases and controls (Table 1). Fifteen (24%) patients were classified as in stage 1 of the Hoehn–Yahr severity scale, 26 (42%) in stage 2, 10 (16%) in stage 3, and 11 (18%) in stages 4 and 5. The mean age of PD onset was 64  ±  6 years and the mean

Discussion

Oxidative stress, characterized by an imbalance between exposure to free radicals or other reactive species and antioxidant defenses, has been implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer and Parkinson disease [13], [14], [16], [17], [18], [19], [40], [41] and it may be related to changes in mitochondrial function and protein clearance [2], [40], [41]. In this study, the systemic rise in multiple markers (such as plasma F2-IsoPs, HETEs, 7β-and

Acknowledgments

We are grateful to Professor Jason Morrow, Dr. Ginger Milne, and the Eicosanoid Core Laboratory at Vanderbilt University for providing the standards for neuroprostane measurement. We are grateful to the Biomedical Research Council (Grant 03/1/21/18/213) and National Medical Research Council (Grant NMRC/1157/2008) for their generous support of this study.

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