An Enriched Environment Ameliorates Oxidative Stress and Olfactory Dysfunction in Parkinson’s Disease with α-Synucleinopathy

Parkinson’s disease (PD) features nonmotor symptoms such as olfactory dysfunction referred to as hyposmia, an initial sign of disease progression. Metabolic dysfunction can contribute to neurodegenerative diseases, and various xenobiotics and endogenous compounds are also involved in the pathogenesis of PD. Although aerobic exercise was found to induce preservation or improvement in olfactory function in PD patients in a recent study, the exact underlying mechanism for this effect is not clear. We aimed to investigate the influence of an enriched environment (EE) on olfactory dysfunction especially via metabolic pathways related to detoxification enzymes. Eight-month-old transgenic (Tg) PD mice that overexpress human A53T α-synuclein (α-syn) were randomly allocated to an EE or standard conditions for 2 mo. The buried food test showed that EE group had significantly improved olfactory function compared to the control group. Reverse transcription polymerase chain reaction (PCR) and real-time quantitative PCR showed that expression of the detoxification enzymes–– cytochrome P450 family 1 subfamily A member 2, paraoxonase 1, alcohol dehydrogenase 1, UDP glucuronosyltransferase family 2 member A1 complex locus, aldehyde oxidase homolog 2, and aldehyde glutathione peroxidase 6––was significantly increased in the olfactory bulb (OB) of the PD control group, but these enzymes were normalized in the EE group. Immunohistochemical staining of the OB showed that oxidative stress and nitrated α-syn were significantly increased in the control group but decreased in the EE group. In conclusion, we suggest that exposure to an EE decreases both oxidative stress and nitrated α-syn, resulting in normalized detoxification enzymes and amelioration of olfactory dysfunction.

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The Possible Role of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 on Locomotor Activity and Oxidative Stress in a Rotenone-Induced Zebrafish Model of Parkinson’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9629102 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Ovidiu-Dumitru Ilie ◽

Emanuela Paduraru ◽

Madalina-Andreea Robea ◽

Ioana-Miruna Balmus ◽

Roxana Jijie ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Locomotor Activity ◽

Prolonged Exposure ◽

Bifidobacterium Longum ◽

The Body ◽

The Other ◽

Control Group

Background. As every organ within the body, the brain is also extremely susceptible to a plethora of noxious agents that change its chemistry. One component frequently found in current products against harmful species to crops is rotenone whose effect under prolonged exposure has been demonstrated to cause neurodegenerative disorders such as Parkinson’s disease. The latest reports have indeed revealed that rotenone promotes Parkinson’s in humans, but studies aiming to show congruent effects in zebrafish (Danio rerio) are lacking. Material and Methods. In this context, the aim of the present study was to demonstrate how chronic administration of rotenone for 3 weeks impairs the locomotor activity and sociability and induces oxidative stress in zebrafish. Results. There were no statistically significant differences following the analysis of their social interaction and locomotor tests ( p > 0.05 ). However, several exceptions have been noted in the control, rotenone, and probiotics groups when we compared their locomotor activity during the pretreatment and treatment interval ( p < 0.05 ). We further assessed the role of rotenone in disturbing the detoxifying system as represented by three enzymes known as superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Despite the fact that there were no statistically significant changes within SOD and GPx levels between the control group and rotenone, probiotics, and rotenone + probiotics ( p > 0.05 ), relevant changes have been observed between the analyzed groups ( p < 0.05 and p < 0.005 , respectively). On the other hand, significant differences ( p < 0.05 ) have been observed for MDA when we analyzed the data between the control group and the other three groups. Conclusions. Our results suggest that rotenone can be successfully used to trigger Parkinson’s disease-related symptomatology in zebrafish.

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Associations between probable REM sleep behavior disorder, olfactory disturbance, and clinical symptoms in Parkinson’s disease: A multicenter cross-sectional study

PLoS ONE ◽

10.1371/journal.pone.0247443 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0247443

Author(s):

Mutsumi Iijima ◽

Yasuyuki Okuma ◽

Keisuke Suzuki ◽

Fumihito Yoshii ◽

Shigeru Nogawa ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Clinical Symptoms ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Olfactory Dysfunction ◽

Olfactory Function ◽

Cross Sectional ◽

Sleep Behavior

Background Rapid eye movement sleep behavior disorder (RBD) and olfactory dysfunction are useful for early diagnosis of Parkinson’s disease (PD). RBD and severe olfactory dysfunction are also regarded as risk factors for cognitive impairment in PD. This study aimed to assess the associations between RBD, olfactory function, and clinical symptoms in patients with PD. Methods The participants were 404 patients with non-demented PD. Probable RBD (pRBD) was determined using the Japanese version of the RBD screening questionnaire (RBDSQ-J) and the RBD Single-Question Screen (RBD1Q). Olfactory function was evaluated using the odor identification test for Japanese. Clinical symptoms were evaluated using the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts I–IV. Results In total, 134 (33.2%) patients indicated a history of pRBD as determined by the RBD1Q and 136 (33.7%) by the RBDSQ-J based on a cutoff value of 6 points. Moreover, 101 patients were diagnosed as pRBD by both questionnaires, 35 by the RBDSQ-J only, and 33 by the RBD1Q only. The MDS-UPDRS parts I–III scores were significantly higher and disease duration significantly longer in the pRBD group. pRBD was significantly associated with male gender and the MDS-UPDRS part I score. The olfactory identification function was significantly reduced in the pRBD group. Conclusions About 33% of the patients with PD had pRBD based on the questionnaires, and both motor and non-motor functions were significantly decreased in these patients. These results suggest that more extensive degeneration occurred in patients with non-demented PD with RBD.

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EEG features in patients with Parkinson's disease during directional perception of olfactory stimuli

Annals of Clinical and Experimental Neurology ◽

10.54101/acen.2021.4.3 ◽

2021 ◽

Vol 15 (4) ◽

pp. 27-35

Author(s):

Sergey P. Kozhevnikov ◽

Irina L. Ivanova ◽

Natalia V. Komissarova ◽

Anastasia V. Shubina ◽

Matvey A. Vlasov

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Right Hemisphere ◽

Olfactory Dysfunction ◽

Olfactory Stimulation ◽

Control Group ◽

Olfactory Perception ◽

Study Results ◽

Olfactory Stimuli ◽

The Right

Introduction. Olfactory dysfunction is considered to be an early and relatively important marker of Parkinson's disease (PD). Olfactory studies using objective neurophysiological methods may become one of the diagnostic tests to identify individuals with a high risk of developing PD. The aim of the study was to assess the spectral and topographic characteristics of bioelectrical brain activity in patients with PD during directional perception of olfactory stimuli. Materials and methods. This study included 30 patients with PD (mean age was 66.5 6.5 years). The control group consisted of 20 people without PD (mean age was 65.3 8.5 years). Lavender oil, clove oil, camphor oil and -mercaptoethanol solution (an aversive stimulus) were used for olfactory stimulation, while distilled water was used as a control test. The test subject sat with their eyes closed and inhaled the presented smell for 30 seconds, while an EEG recording was made during this time. Study results. Olfactory stimulation in patients with PD showed increased synchronicity of the 3 rhythm in the right hemisphere, as well as the rhythm in the parieto-occipital regions of both hemispheres. These changes indicate significant activation of internal (endogenous) attention, increased overall, non-specific readiness potential, as well as the involvement of the limbic-reticular complex in olfactory perception. Olfactory perception in the control group was accompanied by reduction in the 1 rhythm amplitude in the parieto-occipital regions bilaterally, which may indicate moderate activation of external (exogenous) attention and the posterior attention system responsible for simple perception processes. Conclusion. Increased 3 rhythm amplitude in the right hemisphere and increased rhythm amplitude, observed during directional olfactory perception, may indicate olfactory dysfunction and should be viewed as an additional indicator when establishing a diagnosis of Parkinsons disease.

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Parkinsonism-like disease induced by rotenone in rats: Treatment role of curcumin, dopamine agonist and adenosine A2A receptor antagonist

Current Aging Science ◽

10.2174/1874609814666210526115740 ◽

2021 ◽

Vol 14 ◽

Author(s):

Asmaa Fathy Aboul Naser ◽

Wessam Magdi Aziz ◽

Yomna Rashad Ahmed ◽

Wagdy Khalil Bassaly Khalil ◽

Manal Abdel Aziz Hamed

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Inflammatory Mediator ◽

Adenosine A2a Receptor ◽

Control Group ◽

A2a Receptor ◽

Adenosine A2a

Background: Parkinsonism is a neurodegenerative disorder that affects elderly people worldwide. Methods: Curcumin, adenosine A2AR antagonist (ZM241385) and Sinemet® (L-dopa) were evaluated against Parkinson’s disease (PD) induced by rotenone in rats and comparativelyrelatively compared with our previous study on mice model. Results: Rats injected with rotenone showed severe alterations in adenosine A2A receptor gene expression, oxidative stress markers, inflammatory mediator, energetic indices, apoptotic marker and DNA fragmentation levels as compare with the control group. Treatments with curcumin, ZM241385, and Sinemet® restored all the selected parameters. The brain histopathological features of cerebellum regions confirmed our results. By comparing our results with the previous results on mice, we noticed that mice respond to rotenone toxicity and treatments more than rats regarding to behavioral observation, A2AR gene expression, neurotransmitter levels, inflammatory mediator and apoptotic markers, while rats showed higher response to treatments regarding to oxidative stress and energetic indices. Conclusion: Curcumin succeeded to attenuate the severe effects of Parkinson’s disease in rat model and can be consider as a potential dietary supplement. Adenosine A2AR antagonist has almost the same pattern of improvement as Sinemet® and may be considered as a promising therapy against PD. By comparing the role of animal species in response to PD symptoms and treatments, our previous report on mice explore the response of mice to rotenone toxicity than rats, while rats showed higher response to treatments. Therefore, no animal model can perfectly recapitulate all the pathologies of PD.

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Polymorphisms in the genes of citohrom oxidase P450 2D6 (CYP2D6), paraoxonase 1 (PON1) and apolipoproteine E (APOE) as risk factors for Parkinson's disease

Vojnosanitetski pregled ◽

10.2298/vsp0701025d ◽

2007 ◽

Vol 64 (1) ◽

pp. 25-30 ◽

Cited By ~ 9

Author(s):

Gordana Djuric ◽

Marina Svetel ◽

Nikolaevic Illarioskin ◽

Natasa Dragadjevic ◽

Jelena Gavrilovic ◽

...

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Onset ◽

Age At Onset ◽

Paraoxonase 1 ◽

Control Group ◽

Study Results ◽

P450 2D6 ◽

Genotype Ii

Background/Aim. The presence of Parkinson's disease (PD) among the members of a family is a clear indication of the significance of genetics in its development. In spite of that, the majority of patients with PD shows a sporadic form of the disease induced as a result of interaction of both environmental and genetic factors. The aim of this study was to examine the effects of polymorphisms in the genes of cytohrome P450 2D6(CYP2D6), paraoxonase 1 (PON 1) and apolipoprotein E (APOE), as risk factors for PD. Methods. We examined 106 patients with PD (65 men and 41 women) and 75 ethnically matched control subjects. The mean age at onset of PD in the patients was 46.9?9.4 years (ranging from 30 to 70 years). Genotyping was performed using standard PCR amplification and restriction endonuclease digestion protocols described for known polymorphism in the candidate genes under study. Results. The genotype A/A polymorphisms 2D6* gene of CYP2D6 and genotype M/M polymorphisms L54M gene of PON1 were significantly more frequent in the patients with PD than in the control group. The patients with genotypes A/A and M/M had 3.4 and 3.2 higher risk of PD, respectively than the control group (p = 0.01). The relation between genotypes A/A gene of CYP2D6 and M/M gene of PON1 was modified by the age at onset. The genotypes were associated with early onset of PD (p = 0.001, p = 0.004). The carriers of the A and M alleles in homozygote had 2.4 and 4.2 years respectively earlier onset of PD than carriers of other genotypes with these polymorphisms. The frequency allele ?4 gene of APOE was higher in the PD patients with early onset (20%) than in PD with later onset (7.4%), while the genotype ?3/?3 was associated with PD late onset (p = 0.024). Combined genotype I (carriers of the two risk allels in homozygote and one alleles risk in heterozygote) and combined genotype II (carriers of the three alleles risk in homozygote) caused early PD. Combined genotype II was detected in 12.7% of the patients in the group of early onset, and in 2.4% of the patients with the onset after 45 years. Conclusion. The results of our study suggest that the genotypes A/A and M/M genes of CYP2D6 and PON1, and allele ?4 gene are an important risk for the development of PD, causing its early onset. The cumulative effects of the risk genes cause an early onset of PD.

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Orthonasal, but not Retronasal Olfaction Is Specifically Impaired in Parkinson’s Disease

Chemical Senses ◽

10.1093/chemse/bjaa024 ◽

2020 ◽

Vol 45 (5) ◽

pp. 401-406 ◽

Cited By ~ 1

Author(s):

Emilie Aubry-Lafontaine ◽

Cécilia Tremblay ◽

Pascali Durand-Martel ◽

Nicolas Dupré ◽

Johannes Frasnelli

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Olfactory Dysfunction ◽

Olfactory Function ◽

Healthy Controls ◽

Compensatory Mechanisms ◽

Motor Disturbance ◽

Flavor Perception ◽

Olfactory Testing ◽

Retronasal Olfaction

Abstract Olfactory dysfunction (OD) in Parkinson’s disease (PD) appears several years before the presence of motor disturbance. Olfactory testing has the potential to serve as a tool for early detection of PD, but OD is not specific to PD as it affects up to 20% of the general population. Olfaction includes an orthonasal and a retronasal components; in some forms of OD, retronasal olfactory function is preserved. We aimed to evaluate whether combined testing components allows for discriminating between PD-related OD and non-Parkinsonian OD (NPOD). The objective of this study is to orthonasal and retronasal olfactory function in PD patients and compare them to a NPOD group and to healthy controls. We hypothesized that this combined testing allows to distinguish PD patients from both other groups. We included 32 PD patients, 25 NPOD patients, and 15 healthy controls. Both olfactory components were impaired in PD and NPOD patients, compared with controls; however, NPOD patients had significantly better orthonasal scores than PD patients. Furthermore, the ratio of retronasal/orthonasal score was higher in PD than in both other groups. In the NPOD group, orthonasal and retronasal scores were significantly correlated; no such correlation could be observed in PD patients. In summary, PD patients seem to rely on compensatory mechanisms for flavor perception. Combined orthonasal and retronasal olfactory testing may contribute to differentiate PD patients from patients with NPOD.

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Olfactory Dysfunction Predicts Disease Progression in Parkinson’s Disease: A Longitudinal Study

Frontiers in Neuroscience ◽

10.3389/fnins.2020.569777 ◽

2020 ◽

Vol 14 ◽

Author(s):

Runcheng He ◽

Yuwen Zhao ◽

Yan He ◽

Yangjie Zhou ◽

Jinxia Yang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Progression ◽

Rating Scale ◽

Mmse Score ◽

Clinical Manifestations ◽

Olfactory Dysfunction ◽

Olfactory Function ◽

Motor Symptom

Background and Objective:Olfactory dysfunction (hyposmia) is an important non-motor symptom of Parkinson’s disease (PD). To investigate the potential prognostic value of hyposmia as a marker for disease progression, we prospectively assessed clinical manifestations and longitudinal changes of hyposmic PD patients and normosmic ones.MethodsOlfactory function was evaluated with the Sniffin’ Sticks in PD patients at baseline. One hundred five hyposmic PD patients and 59 normosmic PD patients were enrolled and followed up for 2 years. They were subsequently evaluated at baseline and during follow-up periods with neurological and neuropsychological assessments. Clinical manifestations and disease progressions were compared between hyposmic and normosmic patients. In addition, the relationship between disease progressions and olfactory function was analyzed.ResultsOur study suggested that hyposmic PD patients and normosmic ones were similar in gender, age, education levels, age of onset, disease duration, and clinical features at baseline. Hyposmic PD patients exhibited more severe Unified Parkinson’s Disease Rating Scale Part II–III (UPDRS II-III) scores, higher levodopa equivalent dose (LED) needs, and poorer Mini-Mental State Examination (MMSE) score at follow-up visits compared to those in normosmic PD patients. Hyposmia also showed greater rates in the increase of LED needs, improvement of UPDRS III score, and deterioration of MMSE score. Both improvement of UPDRS III score and decline of MMSE score were associated with poorer odor identification.ConclusionOur prospective study demonstrated that hyposmic PD patients showed a relatively worse clinical course compared with normosmic patients. Olfactory dysfunction is a useful predictor of disease progression.

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Functional Optical Hemodynamic Imaging of the Olfactory Cortex in Patients with Parkinson’s Disease

Early Detection and Rehabilitation Technologies for Dementia ◽

10.4018/978-1-60960-559-9.ch022 ◽

2011 ◽

pp. 167-171 ◽

Cited By ~ 2

Author(s):

Masayuki Karaki ◽

Eiji Kobayashi ◽

Ryuichi Kobayashi ◽

Kosuke Akiyama ◽

Tetsuo Toge ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Orbitofrontal Cortex ◽

Near Infrared ◽

Isovaleric Acid ◽

Olfactory Dysfunction ◽

Olfactory Function ◽

Motor Symptom ◽

Test Results ◽

Baseline Values

Olfactory dysfunction is a frequent non-motor symptom in Parkinson’s disease (PD). This symptom is considered to be an early manifestation of the disease. The aim of this study was to establish the cortical basis of olfactory function in patients with PD. This study was conducted on ten healthy, normosmic subjects and seven patients with PD (one with subjective olfactory dysfunction and nine without subjective olfactory dysfunction). We employed a 22-channel near-infrared spectroscopy (NIRS) device with eight light-incident fibers and seven light-detector fibers, each with an inter-optode distance of 2.5 centimeters on the frontal head. Isovaleric acid was used as the odor stimulant. We measured the change in total hemoglobin concentrations (totalHb) from pre-baseline values and compared the results obtained for healthy normosmic subjects and patients with PD. In all healthy normosmic subjects and three patients with PD, isovaleric acid caused remarkable changes in (totalHb), especially in the lower areas of the frontal cortex. However, in four patients with PD, isovaleric acid caused no changes. This result indicates that subjective symptoms are different from objective test results in patients with PD. These activated areas may be related to the orbitofrontal cortex corresponding to the olfactory cortices. This study suggests that normosmic subjects with PD already have damage to their olfactory function.

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Changes in Oxidative Stress Index and Lipid Peroxidation Product in the Brain of Rats with Lesion of Central Dopaminergic System after Propofol Administration*

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0013.2612 ◽

2019 ◽

Vol 73 ◽

pp. 337-343

Author(s):

Ewa Romuk ◽

Wioletta Szczurek ◽

Przemysław Nowak ◽

Magdalena Prudel-Babiuch ◽

Ryszard Szkilnik ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Lipid Peroxidation ◽

Parkinson's Disease ◽

Stress Index ◽

Control Group ◽

Lipid Peroxidation Product ◽

Oxidative Stress Index ◽

Group I ◽

Group Ii

Propofol is a commonly used intravenous anesthetic agent with antioxidant properties. However, the effect of propofol on oxidative stress index (OSI) and lipid peroxidation in Parkinson’s disease is still unknown. The present study aimed to evaluate the effect of propofol on OSI and malondialdehyde (MDA) level in the selected brain regions of the rats with Parkinson’s disease (PD). 32 male Wistar rats were divided into four groups: I- control group, II- group with PD, III-control group with propofol, IV-PD group with propofol. 60mg/kg of propofol was given to the 8-weeks-old rats intraperitoneally, and the selected parts of the rats’ brains (frontal cortex, striatum, thalamus and hippocampus) were isolated after decapitation. The concentration of MDA, which is a marker of lipid peroxidation, and OSI were measured. In group IV compared to group II, was observed a significant MDA level decrease in the cortex (39%, p <0.001), striatum (28%, p <0.001), hippocampus (21%, p <0.05) and thalamus (20%, p <0.05), together with a decreased OSI level in the thalamus (71%, p <0,001), cortex (70%, p <0.05), striatum (65%, p <0.001), and hippocampus (57%, p <0.05). In group III compared to group I was observed decrease in MDA level in the cortex (40%, p <0.001). Propofol inhibits oxidative stress in all the evaluated structures of the rat brain with Parkinson’s disease. There are significant differences in the response of brain tissues to administered propofol between rats with PD and healthy ones.

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Oxidative stress-related biomarkers in Parkinson’s disease: A systematic review and meta-analysis

Iranian Journal of Neurology ◽

10.18502/ijnl.v17i3.373 ◽

2019 ◽

Author(s):

Zeba Khan ◽

Sharique Athar Ali

Keyword(s):

Oxidative Stress ◽

Systematic Review ◽

Parkinson’S Disease ◽

Antioxidant Activity ◽

Parkinson's Disease ◽

Meta Analysis ◽

Random Effect Model ◽

Control Group ◽

Oxidative Stress Markers ◽

Stress Markers

Parkinson’s disease (PD) is a neurodegenerative disease characterized with the loss of dopamine-producing neurons in a mid-brain. This loss is believed to be associated with number of environmental and genetic factors. Oxidative stress is found to be one of the factors responsible for the initiation and progression of PD. However, studies are still continued to confirm the connection and mechanism associated with oxidative stress and PD. This systematic review and meta-analysis aimed to assess the association between oxidative stress markers and PD, and explore factors that may elucidate the contradictions in these results. As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline systematic literature search was carried out. Meta-analysis was carried out on pooled standardized mean differences with 95% confidence interval (CI) of patients with PD and controls using random effect model in comprehensive meta-analysis statistical software. Total 17 studies were included into which 25 oxidative stress markers were analyzed. The results revealed that oxidative stress markers [nitrate and nitric oxide (NO)] and antioxidant markers [total antioxidant status (TAS) and thiols] were not statistically different between the PD and control group (P > 0.05). In case of oxidative stress markers, levels of malondialdehyde (MDA), 8-Oxo-2'-deoxyguanosine (8-oxo-dG), and lipid hydro-peroxide (LPO) were found to be high in patients with PD as compared to controls with P < 0.05, whereas lower levels of antioxidant activity of superoxide dismutase (SOD), glucose 6 phosphate dehydrogenase (G6PD), catalase (CAT), and glutathione peroxidase (GPx) were noticed in the PD group as compared to controls (P < 0.05 for all). From the results, it is concluded that patients with PD have high oxidative stress and lower antioxidant activity, and these studied biomarkers would be used as potential diagnostic tool to measure oxidative stress in patients with PD.

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