Iron and Oxidative Stress in Parkinson's Disease: An Observational Study of Injury Biomarkers

Parkinson's disease (PD) is characterized by progressive motor impairment attributed to progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. In addition to an accumulation of iron, there is also an increased production of reactive oxygen/nitrogen species (ROS/RNS...

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Published in:PloS one Vol. 11; no. 1; p. e0146129
Main Authors: Medeiros, Marcio S, Schumacher-Schuh, Arthur, Cardoso, Andreia Machado, Bochi, Guilherme Vargas, Baldissarelli, Jucimara, Kegler, Aline, Santana, Daniel, Chaves, Carolina Maria Martins Behle Soares, Schetinger, Maria Rosa Chitolina, Moresco, Rafael Noal, Rieder, Carlos R M, Fighera, Michele Rechia
Format: Journal Article
Language:English
Published: United States Public Library of Science 11-01-2016
Public Library of Science (PLoS)
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Summary:Parkinson's disease (PD) is characterized by progressive motor impairment attributed to progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. In addition to an accumulation of iron, there is also an increased production of reactive oxygen/nitrogen species (ROS/RNS) and inflammatory markers. These observations suggest that iron dyshomeostasis may be playing a key role in neurodegeneration. However, the mechanisms underlying this metal-associated oxidative stress and neuronal damage have not been fully elucidated. To determine peripheral levels of iron, ferritin, and transferrin in PD patients and its possible relation with oxidative/nitrosative parameters, whilst attempting to identify a profile of peripheral biomarkers in this neurological condition. Forty PD patients and 46 controls were recruited to compare serum levels of iron, ferritin, transferrin, oxidative stress markers (superoxide dismutase (SOD), catalase (CAT), nitrosative stress marker (NOx), thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP) and vitamin C) as well as inflammatory markers (NTPDases, ecto-5'-nucleotidase, adenosine deaminase (ADA), ischemic-modified albumin (IMA) and myeloperoxidase). Iron levels were lower in PD patients, whereas there was no difference in ferritin and transferrin. Oxidative stress (TBARS and AOPP) and inflammatory markers (NTPDases, IMA, and myeloperoxidase) were significantly higher in PD, while antioxidants FRAP, vitamin C, and non-protein thiols were significantly lower in PD. The enzymes SOD, CAT, and ecto-5'-nucleotidase were not different among the groups, although NOx and ADA levels were significantly higher in the controls. Our data corroborate the idea that ROS/RNS production and neuroinflammation may dysregulate iron homeostasis and collaborate to reduce the periphery levels of this ion, contributing to alterations observed in the pathophysiology of PD.
Bibliography:Conceived and designed the experiments: MRF. Performed the experiments: MRF MSM GVB AMC AK CMMBSC DS JB. Analyzed the data: MSM AS-S CRMR MRF. Contributed reagents/materials/analysis tools: MRF RNM MRCS CRMR. Wrote the paper: MSM AS-S CRMR MRF.
Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0146129