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.

Iron Deposition Leads to Neuronal α-Synuclein Pathology by Inducing Autophagy Dysfunction

“…Oxidative stress has been demonstrated to be an important factor in iron-induced pathologies, serving as a link between iron deposition and PD (16, 17). Elevated iron levels in the SN lead to the generation of reactive oxygen species (ROS), such as superoxide anion radicals and hydroxyl radicals; the increase in ROS level subsequently results in the aberrant upregulation of α-synuclein and damage to dopaminergic neurons in PD (16, 17).…”

“…Elevated iron levels in the SN lead to the generation of reactive oxygen species (ROS), such as superoxide anion radicals and hydroxyl radicals; the increase in ROS level subsequently results in the aberrant upregulation of α-synuclein and damage to dopaminergic neurons in PD (16, 17). In the presence of iron, the highly reactive hydroxyl radical is produced by the Fenton reaction (16).…”

Sleep Disturbance and Serum Ferritin Levels Associate with High Impulsivity and Impulse Control Disorders in Male Parkinson’s Disease Patients

“…Studies examining serum levels of ferritin in PD patients have been inconclusive, showing either increased levels [17], or no significant relationship [18,19]. Ferritin levels have been reported to be increased in both male and female PD patients when compared to controls, correlating with Hoehn & Yahr stage and disease duration [20].…”

Effects of Medium Molecular Weight Heparinyl Phenylalnine on Superoxide Dismutase Activity in Mice

“…Recently, participation of free radicals is reported in several diseases, such as in the cardiovascular system (14), Alzheimer's disease (15), arteriosclerosis (16), myocardial infarction (17), cerebral infarction (18), Parkinson's disease (19), pancreatitis (20), glomerulonephritis (21), diabetes (22), cirrhosis (23), stomach ulcers (24), atopic dermatitis (25) and asthma (26,27). Although the research on EC-SOD is advanced and several radical scavengers are under in vivo 30: 841-844 (2016) development, the number of ethical drugs is few.…”