Influence of Therapy on Some Important Final Products of Oxidation of Lipids, Proteins and Nucleic Acids in Patients with Parkinson’s Diseases (original) (raw)
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Peripheral markers of oxidative stress in Parkinson’s disease. the role of L-DOPA
Free Radical Biology and Medicine, 1999
Oxidative stress plays a central role in the pathogenesis of Parkinson's disease (PD). L-DOPA, the gold standard in PD therapy, may paradoxically contribute to the progression of the disease because of its pro-oxidant properties. The issue, however, is controversial. In this study, we evaluated peripheral markers of oxidative stress in normal subjects, untreated PD patients and PD patients treated only with L-DOPA. We also measured platelet and plasma levels of L-DOPA, 3-O-methyldopa (the long-lasting metabolite of the drug), and dopamine. We found that isolated platelets of treated PD patients form higher amounts of 2,3-dihydroxybenzoate, an index of hydroxyl radical generation, than platelets of controls or untreated patients. In treated patients, platelet levels of 2,3-dihydroxybenzoate were positively correlated with platelet levels of L-DOPA, 3-O-methyldopa, and with the score of disease severity. Disease severity was correlated with platelet and plasma levels of L-DOPA, as well as with the daily intake of the drug. No significant differences in platelet levels of cytosolic and mitochondrial isoforms of the antioxidant enzyme superoxide dismutase were found between PD patients, either treated or untreated, and controls. Our findings lend further support to the hypothesis that L-DOPA might promote free radical formation in PD patients.
Plasma lipid peroxidation in sporadic Parkinson's disease. Role of the l-dopa
Journal of The Neurological Sciences, 2006
Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease (PD). There are several methods to measure oxidative stress, being lipid peroxidation (LPO) one of the most frequently used. Endogenous plasma LPO was determined by a spectrofluorimetric method in fifty two patients with sporadic PD and in forty controls. To know the maximum capacity of lipids to peroxidate, LPO was also measured after co-incubation with Fe 2+ /H 2 O 2 (exogenous LPO). All PD patients were taken l-dopa and the effect of this treatment on LPO levels was additionally studied. Urine catecholamines and their main metabolites were also analyzed, and their possible correlation to LPO statistically studied. Endogenous plasma LPO levels were 33% higher in PD group than in control group ( P < 0.001). Exogenous plasma or oxidizability was also higher in PD patients compared to controls (20%, P < 0.05). The intake of l-dopa was negatively dose-related to endogenous and exogenous plasma LPO. In conclusion, plasma of PD patients has elevated levels of LPO and also is more prone to peroxidation than that in the control group. The results also suggest an antioxidant effect of l-dopa. D
Neurobiology of Disease, 2004
We determined systemic oxidative stress in Parkinson's disease (PD) patients, patients with other neurological diseases (OND) and healthy controls by measurement of in vitro lipoprotein oxidation and levels of hydro-and lipophilic antioxidants in plasma and cerebrospinal fluid (CSF). Additionally, we investigated the influence of levodopa (LD) and dopamine agonist therapy (DA) on the oxidative status in PD patients. We found increased oxidative stress, seen as higher levels of lipoprotein oxidation in plasma and CSF, decrease of plasma levels of protein sulfhydryl (SH) groups and lower CSF levels of A-tocopherol in PD patients compared to OND patients and controls. Levodopa treatment did not significantly change the plasma lipoprotein oxidation but LD monotherapy tended to result in an increase of autooxidation and in a decrease of plasma antioxidants with significance for ubiquinol-10. DA monotherapy was significantly associated with higher A-tocopherol levels. Patients with DA monotherapy or co-medication with DA showed a trend to lower lipoprotein oxidation. These data support the concept of oxidative stress as a factor in the pathogenesis of PD and might be an indicator of a potential prooxidative role of LD and a possible antioxidative effect of DA in PD treatment. D
Oxidative damage in Parkinson disease: Measurement using accurate biomarkers
Free Radical Biology and Medicine, 2010
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 F 2 -isoprostanes (F 2 -IsoPs), hydroxyeicosatetraenoic acid products (HETEs), cholesterol oxidation products, neuroprostanes (F 4 -NPs), phospholipase A 2 (PLA 2 ) 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 F 2 -IsoPs, HETEs, 7β-and 27-hydroxycholesterol, 7-ketocholesterol, F 4 -NPs, and urinary 8-OHdG were elevated, whereas the levels of plasma PLA 2 and PAF-AH activities were lower, in PD patients compared to controls (p b 0.05). The levels of plasma F 2 -IsoPs, HETEs, and urinary 8-OHdG were higher in the early stages of PD (p trend b 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.
PERIPHERAL MARKERS FOR OXIDATIVE STRESS IN PARKINSON’S DISEASE PATIENTS OF EASTERN INDIA
Oxidative stress is thought to play a major role in the pathogenesis of Parkinson’s disease (PD). Neurons are highly susceptible to a defective antioxidant scavenging system, thus inducing oxidative changes in human red blood cells (RBCs), in vivo and in vitro. Previous studies on oxidative stress in RBCs in patients with PD have yielded controversial results claiming unaltered activity to reduced activity. We have thus undertaken this study to investigate the possibility of oxidative damage to the RBCs in PD by measuring the cytosolic antioxidant enzymes viz., catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (G-Px). The biochemical parameters were measured in erythrocytes of 80 PD patients and 80 normal age matched healthy controls. The enzymes activities were correlated with age of patients, age of onset of disease, duration of disease, United Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr stage. Patients with PD had higher red blood corpuscle (RBC) activity of SOD. The CAT, and G-Px activities were significantly lower in patients with PD compared to the controls. Erythrocyte SOD, CAT and G-Px were markedly lower in those PD patients who were suffering for a greater duration of the disease and in advanced cases of PD. A significant (P < 0.05) negative correlation of enzyme activities with disease duration, UPDRS score and Hoehn and Yahr stage of the disease was found. Results of our present study concludes the implication of oxidative stress as one of the risk factors, which can initiate or promote neurodegeneration in PD by playing a role in dopaminergic neuronal loss and was correlated to the severity of the disease.
Molecular Effects of L-dopa Therapy in Parkinson’s Disease
Current Genomics, 2014
Parkinson's disease (PD) is one of the most common neurological diseases in elderly people. The mean age of onset is 55 years of age, and the risk for developing PD increases 5-fold by the age of 70. In PD, there is impairment in both motor and nonmotor (NMS) functions. The strategy of PD motor dysfunction treatment is simple and generally based on the enhancement of dopaminergic transmission by means of the L-dihydroxyphenylalanine (L-dopa) and dopamine (DA) agonists. L-dopa was discovered in the early-60's of the last century by Hornykiewicz and used for the treatment of patients with PD. L-dopa treatment in PD is related to decreased levels of the neurotransmitter (DA) in striatum and absence of DA transporters on the nerve terminals in the brain. L-dopa may also indirectly stimulate the receptors of the D1 and D2 families. Administration of L-dopa to PD patients, especially long-time therapy, may cause side effects in the form of increased toxicity and inflammatory response, as well as disturbances in biothiols metabolism. Therefore, in PD patients treated with L-dopa, monitoring of oxidative stress markers (8-oxo-2'-deoxyguanosine, apoptotic proteins) and inflammatory factors (high-sensitivity C-reactive protein, soluble intracellular adhesion molecule), as well as biothiol compounds (homocysteine, cysteine, glutathione) is recommended. Administration of vitamins B6, B12, and folates along with an effective therapy with antioxidants and/or anti-inflammatory drugs at an early stage of PD might contribute to improvement in the quality of the life of patients with PD and to slowing down or stopping the progression of the disease.
Plasma oxidative and inflammatory markers in patients with idiopathic Parkinson’s disease
Acta Neurologica Belgica, 2012
Parkinson's disease (PD) is the most common neurodegenerative disorder after alzheimer's disease. Neuroinflammation and oxidative damage are implicated to be responsible for the pathogenesis of neurodegenerative diseases. However, there are a few studies showing the changes in the biomarkers for neuroinflammation and oxidative damage in neurodegenerative diseases. In our study we aimed to examine the role of the molecules that are involved in oxidative stress and inflammation in PD patients taking L-dopa treatment. Oxidized-LDL (ox-LDL), high-sensitivity C-reactive protein (hs-CRP) and the soluble intracellular adhesion molecule (ICAM) were chosen as biomarkers for systemic inflammation and oxidative damage. The patients were classified according to the Hoehn-Yahr staging system. Forty-five idiopathic L-dopa-given PD patients and 25 age-matched healthy controls were examined. Plasma ox-LDL and ICAM levels were significantly higher in PD patients when compared with controls (p \ 0.001 and p \ 0.05, respectively). PD patients at all stages had significantly higher plasma ox-LDL levels than controls (p \ 0.001). Plasma ICAM levels at stage 1 and 2 and CRP levels at stage 2 patients were significantly higher than controls (p \ 0.05, p \ 0.05, and p \ 0.01, respectively). We insist that further studies have to be conducted to establish neuroinflammation and oxidative damage in PD. Establishing the roles of these pathological processes in PD might be the key to effective therapy at an early stage by antioxidants and/or anti-inflammatory drugs.
Antioxidant therapy in Parkinson's disease
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 1987
It is postulated that endogenous oxidative mechanisms are a major factor in the continuing death of dopaminergic neurons and the progression of Parkinson's disease. Scientific evidence in support of, and negating, the free radical auto-toxicity and dopamine toxicity concepts is reviewed. There is conflicting evidence whether free radicals are involved in the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and attempts to prevent the toxicity of MPTP with antioxidant therapy have had variable results. The oxidation of dopamine by monoamine oxidase produces toxic metabolites however animal studies with high dose longterm levodopa and MPTP have failed to show clear evidence for autoxidation. Firm supportive evidence is obtained from the monoamine oxidase B inhibitor experience which demonstrated a block of the toxicity of MPTP in animals and probable prolongation of the course of human Parkinson's disease. The scientific data available is inconclusive but there ...
Antioxidants
Parkinson’s disease (PD) is a chronic neurodegenerative condition affecting more than 1% of people over 65 years old. It is characterized by the preferential degeneration of nigrostriatal dopaminergic neurons, which is responsible for the motor symptoms of PD patients. The pathogenesis of this multifactorial disorder is still elusive, hampering the discovery of therapeutic strategies able to suppress the disease’s progression. While redox alterations, mitochondrial dysfunctions, and neuroinflammation are clearly involved in PD pathology, how these processes lead to the preferential degeneration of dopaminergic neurons is still an unanswered question. In this context, the presence of dopamine itself within this neuronal population could represent a crucial determinant. In the present review, an attempt is made to link the aforementioned pathways to the oxidation chemistry of dopamine, leading to the formation of free radical species, reactive quinones and toxic metabolites, and susta...