Neutrophil function, nitric oxide, and blood oxidative stress in Parkinson's disease

Abstract

We studied nitrogen radical nitric oxide (.NO) release and reactive oxygen species (ROS) production by isolated neutrophils after phorbol myristate acetate (PMA) stimulation in 12 newly diagnosed and nine treated Parkinson's disease (PD) patients and 10 age-matched healthy controls. Neutrophils of both groups of PD patients had an elevated PMA-activated release of .NO [61 and 57%, respectively, higher than that of controls (p < 0.05)]. In contrast, H2O2 release was only significantly increased by 56% in chronically treated patients. In agreement, the maximum rate of luminol-dependent chemiluminescence, which partly represents O2- H2O2- .NO interactions, was increased only in the treated group. When other blood markers of oxidative stress were compared, only erythrocyte catalase activity was decreased in both PD patient series by 33 and 39%, respectively (p < 0.05), whereas plasma antioxidant capacity and erythrocyte superoxide dismutase activity levels were decreased only in treated PD patients. This study suggests that neutrophils express a primary alteration of .NO release in PD patients, whereas H2O2 and oxidative-stress parameters are more probably related to the evolution of PD or to effects of treatment with L-dopa.

Association of Polymorphism of Neuronal Nitric Oxide Synthase Gene with Risk to Parkinson’s Disease

“…Nitrite content was increased in PD patients that carry any genotype of nNOS exon 29 or heterozygous variant genotype of exon 18 as compared with respective controls. This is in accordance with the previous studies that have shown an increased nitrite content and nNOS activity in the PMNs of PD patients [28,29]. Such observations suggest that nNOS exon 29 polymorphism and heterozygous variant of exon 18 could be associated with PD risk.…”

Effect of Sesamol in Association With Folic Acid on 6-Ohda Induced Parkinsonian Animals- Biochemical, Neurochemical and Histopathological Evidence

“…Oxidative stress is the basic precursor for almost all the deadly diseases and PD is also one among them [3]. Thus, it has been focused to find natural antioxidants such as curcumin, epigallocatechin-3-gallate, melatonin and so on to treat PD [4].…”

Free Radicals, Oxidative Stress and Oxidative Damage in Parkinson's Disease

“…Metabolic alterations in circulating blood cells are widely accepted as representative of similar central nervous system changes in human PD. Increased NO release of neutrophils and decreased catalase activity in erythrocytes were observed at the beginning of PD; H 2 O 2 release by neutrophils and mitochondrial impaired function may be later signs in PD (Gatto et al, 1996).…”

“…Oxidative stress promotes aggregation and accumulation of -synuclein, characteristic of Parkinson's disease (Kozlowski et al, 2009;Opazo et al, 2003). The series of observed changes include glycation protein oxidation, lipid peroxidation, depletion of antioxidants and nucleic acid oxidation (Famulari et al, 1996;Gatto et al, 1996;Gatto et al, 1997;Repetto et al, 1999;Fiszman et al, 2003;Repetto, 2008). It has been proposed that oxidative damage favors the aggregation of -synuclein in sporadic PD.…”

“…Oxidative damage is characterized by increases in the levels of the oxidation products of macromolecules, such as thiobarbituric acid reactive substances (TBARS), and protein carbonyls. Oxidative stress, to which neurons are highly susceptible, is also known to induce oxidative changes in human red blood cells (RBCs), in vivo and in vitro (Gatto et al, 1996;Repetto & Llesuy, 2004, Repetto, 2008. Based on the hypothesis that oxidative changes are not organ specific, their activities may be evaluated in peripheral and red blood cells.…”