title: Iron and Oxidative Stress in Parkinson's Disease: An Observational Study of Injury Biomarkers.
abstract: 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.
authors.affiliation: Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Marcio S
authors.initials: MS
authors.lastname: Medeiros
authors.affiliation: Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Arthur
authors.initials: A
authors.lastname: Schumacher-Schuh
authors.affiliation: Natural and Exact Sciences Center, Graduate Program in Life Sciences: Toxicological Biochemistry, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Andreia Machado
authors.initials: AM
authors.lastname: Cardoso
authors.affiliation: Department of Clinical and Toxicological Analyses, Universidade Federal de Santa Maria, Health Sciences Center, Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Guilherme Vargas
authors.initials: GV
authors.lastname: Bochi
authors.affiliation: Natural and Exact Sciences Center, Graduate Program in Life Sciences: Toxicological Biochemistry, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Jucimara
authors.initials: J
authors.lastname: Baldissarelli
authors.affiliation: Natural and Exact Sciences Center, Graduate Program in Life Sciences: Toxicological Biochemistry, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.|Neuropsychiatry Department, University Hospital, Universidade Federal de Santa Maria, Health Sciences Center, Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Kegler
authors.affiliation: Neuropsychiatry Department, University Hospital, Universidade Federal de Santa Maria, Health Sciences Center, Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Santana
authors.affiliation: Neuropsychiatry Department, University Hospital, Universidade Federal de Santa Maria, Health Sciences Center, Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Carolina Maria Martins Behle Soares
authors.initials: CM
authors.lastname: Chaves
authors.affiliation: Natural and Exact Sciences Center, Graduate Program in Life Sciences: Toxicological Biochemistry, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Maria Rosa Chitolina
authors.initials: MR
authors.lastname: Schetinger
authors.affiliation: Department of Clinical and Toxicological Analyses, Universidade Federal de Santa Maria, Health Sciences Center, Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Rafael Noal
authors.initials: RN
authors.lastname: Moresco
authors.affiliation: Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Carlos R M
authors.initials: CR
authors.lastname: Rieder
authors.affiliation: Natural and Exact Sciences Center, Graduate Program in Life Sciences: Toxicological Biochemistry, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.|Neuropsychiatry Department, University Hospital, Universidade Federal de Santa Maria, Health Sciences Center, Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Michele Rechia
authors.initials: MR
authors.lastname: Fighera
mesh_terms: D015720:5'-Nucleotidase / Q000097:blood; D000243:Adenosine Deaminase / Q000097:blood; D000251:Adenosine Triphosphatases / Q000097:blood; D062107:Advanced Oxidation Protein Products / Q000097:blood; D000368:Aged; D001205:Ascorbic Acid / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002374:Catalase / Q000097:blood*; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000097:blood* / Q000473:pathology; D065842:Pars Compacta / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000097:blood; D026361:Reactive Nitrogen Species / Q000097:blood*; D017382:Reactive Oxygen Species / Q000097:blood*; D013438:Sulfhydryl Compounds / Q000097:blood; D013482:Superoxide Dismutase / Q000097:blood*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
chemical_list: D062107:Advanced Oxidation Protein Products; D015415:Biomarkers; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D014168:Transferrin; D005293:Ferritins; D007501:Iron; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase; D000251:Adenosine Triphosphatases; D001205:Ascorbic Acid