|
 |
| ORIGINAL ARTICLE |
|
| Year : 2014 | Volume
: 4
| Issue : 3 | Page : 146-152 |
|
Alteration in antioxidants level and lipid peroxidation of patients with neurodegenerative diseases {Alzheimer's disease and Parkinson disease}
Ogunro Paul Sunday1, Mustapha F Adekunle2, Oshodi T Temitope3, Adebayo A Richard4, Atiba Adeniran Samuel1, Akande Joel Olufunminyi1, Oke Olufunke Elizabeth1
1 Department of Chemical Pathology, College of Health Sciences, Ladoke Akintola University of Technology, Osogbo, Osun, Nigeria
2 Department of Medicine, Neurology Unit, College of Health Sciences, Ladoke Akintola University of Technology, Osogbo, Osun, Nigeria
3 Department of Clinical Pathology, Lagos University Teaching Hospital, Idi Araba, Nigeria
4 Department of Clinical Pathology, Neuropsychiatric Hospital, Yaba, Lagos, Nigeria
| Date of Submission | 16-Jan-2014 |
| Date of Acceptance | 25-Feb-2014 |
| Date of Web Publication | 16-May-2014 |
Correspondence Address:
Ogunro Paul Sunday
Department of Chemical Pathology, College of Health Science, Ladoke Akintola University of Technology, Osogbo
Nigeria
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2231-0738.132671
 Abstract | | |
Objective: To assess the level of oxidative stress (OS) and the antioxidants that play a prominent role in OS of neurodegenerative diseases; also to test the hypothesis that OS is associated with neuronal degeneration in patients with neurodegenerative diseases {Parkinson's Disease (PD) and Alzheimer's Disease (AD)}. Materials and Methods: A total of 28 AD, 42 PD patients and 42 healthy controls aged 60-80 yrs were recruited for the study. Plasma total antioxidant status (TAS), erythrocyte malondialdehyde (MDA) and glutathione (GSH) concentrations were determined. Erythrocyte antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glucose-6-phosphate dehydrogenase (G6PD) were measured by using standard methods. Results: Plasma TAS was significantly reduced (P < 0.05) in AD and PD subjects when compared with the controls. Erythrocyte antioxizdant enzymes activities of SOD, GSH-Px, CAT and activity of G6PD were significantly reduced (P < 0.01) in AD and PD when compared with that of controls. However, erythrocyte level of MDA in AD and PD subjects were significantly increased (P < 0.01) compared to the controls. Erythrocyte GSH level was significantly reduced (P < 0.01) in AD subjects and (P < 0.05) in PD subjects when compared with the control. Strong significant (P < 0.01) correlation was obtained between the marker of OS (MDA) and SOD among PD and AD patients. Conclusion: The present study reveals elevated OS and strong correlation between SOD and MDA. This indicates that reduced SOD plays a prominent role in the increase of OS in neuronal degeneration. Keywords: Antioxidants, lipid peroxidation, neurodegerative diseases
How to cite this article:
Sunday OP, Adekunle MF, Temitope OT, Richard AA, Samuel AA, Olufunminyi AJ, Elizabeth OO. Alteration in antioxidants level and lipid peroxidation of patients with neurodegenerative diseases {Alzheimer's disease and Parkinson disease}. Int J Nutr Pharmacol Neurol Dis 2014;4:146-52 |
How to cite this URL:
Sunday OP, Adekunle MF, Temitope OT, Richard AA, Samuel AA, Olufunminyi AJ, Elizabeth OO. Alteration in antioxidants level and lipid peroxidation of patients with neurodegenerative diseases {Alzheimer's disease and Parkinson disease}. Int J Nutr Pharmacol Neurol Dis [serial online] 2014 [cited 2023 Feb 1];4:146-52. Available from: https://www.ijnpnd.com/text.asp?2014/4/3/146/132671 |
| Introduction | |  |
Free radicals are molecules with unpaired electron in their outer orbit. Free radicals have very important role in origin of life and biological evolution, having beneficial. effects on the organisms. They pose a serious threat to vital organs, tissues, polyunsaturated fatty acids (PUFAs) of cell membranes and nucleic acids of cells. [1] The activities of free radicals in many age-related diseases have long been of interest, and there is substantial evidence linking cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases (Alzheimer's and Parkinson's disease), rheumatoid arthritis, ischemic/reperfusion injury, obstructive sleep apnea, cardiovascular disease, hypertension and ageing to free radical-induced alterations. [2],[3]
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by cognitive and memory decline, speech loss and personality changes resulting in severe dementia; it is one of the major cause of admissions to nursing homes. [4] AD affects 6-8% of the population aged 65 years and 30% of the population aged 85 years. [5] To date, despite intensive efforts, the pathogenesis of AD remains elusive, and this incomplete understanding of disease pathogenesis has greatly affected the development of accurate animal and cellular models, and thereby retarded the development of therapeutic modalities. Several independent hypotheses have been proposed to link the pathologic lesions and neuronal cytopathology with, among others, apolipoprotein E genotype, [6] hyperphosphorylation of cytoskeletal proteins and amyloid-β metabolism. [7],[8] However, none of these hypotheses alone is sufficient to explain the diversity of biochemical and pathologic abnormalities of AD, which involve a multitude of cellular and biochemical changes. [9],[10],[11] The biochemical mechanism of the pathogenesis of this disease is still unknown, but there is accumulating evidence that suggests a key role of oxidative stress in the pathophysiology of AD. Free radicals produced during oxidative stress are speculated to be pathologically important in AD and other neurodegenerative diseases. [12] Studies have shown that the increase in the level of oxidized protein in Alzheimer's disease is associated with loss of the activity of the 20S proteasome, which represents a major enzyme for the degradation of oxidized proteins. [13],[14] The current research in AD is mainly focused in the post-mortem characterization of the biochemical and pathological alterations present in the brain. [15] Studies in plasma and cerebrospinal fluid of AD patients for the evaluation of the levels of specific vitamins or antioxidants and biomarkers of lipid peroxidation are scanty.
Parkinson's disease (PD) is the second most common neurodegenerative disorder after AD, affecting approximately 1 per cent of the population older than 50 years. [16] Parkinson's disease is a chronic neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The development of PD in patients becomes clinically apparent with severe motor symptoms, including uncontrolled resting tremor, bradykinesia, rigidity, and postural imbalance. [17] In most cases, these symptoms appear after 70-80% of SNpc dopaminergic neurons are lost. [18] The exact etiology of PD remains unclear, but what is clearly known is that the disease is of multi-factorial in nature, including both environmental and genetic factors, which result in development of oxidative stress in specific areas of the brain. [19] Some hypotheses try to explain the nature and causes of this type of cell degeneration. Several studies show that oxidative stress (OS) and mitochondrial dysfunction are two cardinal factors, leading to the development of this process. [20],[21] Current concepts of the pathogenesis of PD center on the formation of reactive oxygen species and the onset of oxidative stress leading to oxidative damage to SNpc.
There are reports suggesting a decrease in antioxidant capacity and other antioxidant enzyme activities with increase in various markers of lipid peroxidation in neurodegenerative diseases. [22],[23] Although the changes in lipid peroxidation and antioxidant defenses are documented in the SNpc of PD patients, the studies of the central nervous system (CNS) are beset with the complexity of direct investigation because of the inaccessibility of the neural tissue, and hence the difficulty in obtaining a brain biopsy, until after the death of the afflicted individual. [23]
In healthy tissues, one of the main sources of free radicals is the mitochondria. This is because these organelles are responsible for more than 90% of cellular oxygen consumption and the radicals in biological systems always, ultimately are generated by the metabolism of oxygen by this route. However, over the course of evolution, cells have constructed enzymatic machinery to combat oxidative stress. For example, superoxide dismutase (SOD) is an enzyme that catalyzes the reaction of the superoxide radical (O 2· - ) to hydrogen peroxide and molecular oxygen (O 2 .) is found in the matrix of mitochondria, which is the site of oxidative phosphorylation. [24] Catalase (CAT) and glutathione peroxidase (GSH-Px) are two other antioxidant enzymes that catalyze the reaction of hydrogen peroxide to molecular oxygen and water, thereby reducing a major source of oxidative stress. All of these enzymes have been shown to confer protection to the neurons against oxidative stress. It is therefore imperative to develop suitable peripheral markers, which can help in the diagnosis and monitoring of neurodegenerative diseases during life. Hence, the aim of the study is to assess the antioxidants capacity and the antioxidants that play a prominent role in development of oxidation stress in the blood of neurodegenerative diseases (AD and PD) patients; and also the level of correlation between antioxidants and marker of oxidative stress.
| Materials and methods | | |
Subjects
The protocol for the study was approved by the Ethical Committee of the Ladoke Akintola University of Technology, College of Health Sciences, Osogbo and Lagos University Teaching Hospital, Lagos, Nigeria. A total of 28 AD patients and 42 PD patients aged 60-80 yrs were recruited from the Neurology Unit of the Department of Internal Medicine of the teaching hospitals. Diagnosis of AD was made using the National Institute for Neurological Disorders/Alzheimer's Disease and Related Disorders (NINDS/ADRDA) [25] criteria. Whereas, the diagnostic criteria for PD were based on the UK PD society brain bank [26] and the selection of PD subjects were based on the following inclusion criteria: tremor, muscular rigidity, brady kinesia, loss of postural reflexes and the phenomenon of freezing foot. The exclusion criteria include vertical gaze impairment, marked autonomic disturbance, bladder and bowel involvements, secondary Parkinsonism More Details, associated dementia, apraxia or pseudobulbar palsy and patients on antipsychotic drugs. The 42 healthy control subjects belong to the same social, age/sex and ethnic background who were recruited from the general population. These control subjects were recruited based on their medical history and physical examination. Their cognitive function was assessed using mini-mental state examination (MMSE) [27] and they did not show signs of dementia.
Analytical procedure
After explaining the rationality of the study, written/informed consent was obtained from the subjects/careers prior to their inclusion in the study. About 10 ml of venous blood was collected after an overnight fast from the venous vein at the antecubital fossa without stasis. Blood samples were collected by venipuncture into vacutainer tubes containing lithium heparin and were centrifuged at 2000 g for 10 min. The plasma was carefully removed and the erythrocyte pellet was washed twice with equal volumes of saline and centrifuged at 2000 g for 15 min. The washed red blood cells were then hemolyzed in distilled water (1:4, v/v) and by freezing and thawing. The hemolyzate was centrifuged and the supernatant and plasma were then stored at -20°C until they were analyzed.
Glucose-6-phosphate dehydrogenase (G6PD) activities were assayed according to the procedure described by Beutler. [28] Malondialdehyde (MDA) level was determined using the method of Draper and Hadley [29] based on the reaction of MDA with thiobarbituric acid (TBA) at 95°C. In the TBA test reaction, MDA and TBA react to form a pink pigment with an absorption maximum at 532 nm. The reaction was performed at pH 2-3 at 95°C for 15 min. The sample was mixed with 2.5 volumes of 10% (w/v) trichloroacetic acid to precipitate the protein. The precipitate was pelleted by centrifugation and an aliquot of supernatant was reacted with 0.67% TBA in a boiling water-bath for 15 min. After cooling, the absorbance was read at 532 nm. Arbitrary values obtained were compared with a series of standard solutions (1, 1, 3, 3 tetramethoxypropane).
Measurement of total antioxidant status (TAS) in the plasma was performed by using a method contained in the commercial kit from Randox Laboratories (Randox Laboratories Ltd, Diamond Road, Crumlin, Co. Antrim, Ireland). [30] The assay was calibrated using 6-hydroxy-2, 5, 8-tetra-methylchroman-2-carboxylic acid (trolox). The results were expressed as mmol/L of trolox equivalent. Measurement of erythrocyte GSH-Px (EC # 1.11.1.9) activity was performed using a commercial kit RANSEL from Randox Laboratories (Randox Laboratories Ltd, Diamond Road, Crumlin, Co. Antrim, Ireland). GSH-Px catalyses the oxidation of glutathione (GSH) to glutathione disulphide (GSSG) by cumenehydroperoxide, in the presence of glutathione reductase and nicotinamide adenine dinucleotide phosphate (NADPH), GSSG is immediately converted to GSH with a concomitant oxidation of NADPH to Nicotinamide adenine dinucleotide phosphate (NADP + ) according to the method of Paglia and Valentine. [31] SOD (EC. 1.15.1.1) activity was assayed by employing xanthine/xanthine oxidase assay commercial kit RANSOD from Randox Laboratories (Randox Laboratories, Crumlin, Antrim, UK). [32] The results of SOD activity were normalized to the hemoglobin content in the erythrocyte lysate and expressed as U/gHb. GSH concentration in erythrocytes was determined using Glutathione Assay Kit; GSH reductase converts oxidized GSH in the sample to reduce GSH. Reaction with reduced GSH, Ellman's Reagent [5, 5'-dithiobis (2-nitrobenzoic acid)] releases a colored product, monitored at 415 nm using a microplate reader. The intensity of the color produced is proportional to GSH concentration, and the calculations were made according to the model curve for GSH, and expressed in μmoles GSH/g Hb. [33] The CAT (EC 1.11.1.6) peroxidative activity was measured by the reaction of formaldehyde produced from methanol with Purpald to produce a chromophore according to the method of Johansson and Hakan Borg; [34] activity was quantified by measuring the absorbance at 540 nm and comparing the results with those obtained with formaldehyde calibrators.
Statistical analysis
Statistical analysis was done with the SPSS version 11 software. All data were expressed as mean ± SD. Statistical significance was analyzed with the paired Student's t-test. Correlations were performed by Pearson's method. P value of less than 0.05 was considered statistically significant.
| Results | | |
The anthropometric measurements and physical clinical parameters of AD and PD subjects and the controls are presented in [Table 1]. Both the subjects and the control are normotensive. The mean ± SD of biochemical parameters are shown in [Table 2]; plasma concentration of TAS of 1.03 ± 0.08 mmol/L trolox equivalent for AD subjects and 1.16 ± 0.12 mmol/L trolox equivalent for PD subjects were significantly reduced (P < 0.05) compared to the control. However, the erythrocytes MDA of 4.63 ± 0.95 nmol/ml for AD subjects and 5.63 ± 0.74 nmol/ml for PD subjects were significantly increased (P < 0.01) compared to the control. The mean activity of G6PD of 8.79 ± 1.51 U/gHb for AD subjects and 9.04 ± 1.05 U/gHb for PD subjects were significantly reduced (P < 0.01) compared to the control. The erythrocytes activities of antioxidant enzymes GSH-Px, SOD and CAT were 39.71 ± 3.82 U/gHb, 675.16 ± 87.07 U/gHb and 859.05 ± 87.74 U/gHb respectively for AD subjects and 37.80 ± 5.37 U/gHb, 704.82 ± 98.19 U/gHb and 909.27 ± 89.31 U/gHb respectively for PD subjects and were significantly reduced (P < 0.01) compared to the control. Likewise, the erythrocytes concentration of GSH (3.37 ± 0.62 μmol/g Hb) for the AD subjects was significantly reduced (P < 0.01) compared to the control and 4.09 ± 0.97 μmol/g Hb for PD subjects was also significantly reduced (P < 0.05) compared to the control. | Table 1: Clinical parameters of neurodegenerative diseases and controls
Click here to view |
 | Table 2: The (mean±SD) plasma concentrations of measured biochemical parameters of the subjects and the controls
Click here to view |
A negative correction was obtained between GSH-Px and MDA (r = -0.3642, P = 0.019) for AD subjects and (r = -0.3927, P = 0.0154) for PD subjects. Likewise, a strong negative correlation was obtained between SOD and MDA (r = -0.4759, P = 0.0092) for AD subjects and (r = -0.4855, P = 0.0086) for PD subjects. Similarly, a negative correlation was obtained between CAT and MDA (r = -0.2851, P = 0.0436) for AD subjects and (r = -0.3758, P = 0.0186) for the PD subjects. A negative correlation was also obtained between CAT and MDA (r = -0.3057, P = 0.0239) for AD subjects and (r = -0.3253, P = 0.0209) for the PD subjects. [Figure 1] shows the comparison between the measured biochemical parameters of the subjects and the controls in graphical form [Table 3]. | Figure 1: Levels of biochemical parameters for the subjects and the controls
Click here to view |
| Discussion | | |
Oxidative stress, characterized by an imbalance between exposure to free radicals or other reactive species and antioxidant defenses, has been implicated in the pathogenesis of neurodegenerative diseases such as AD and PD [2],[3] and it may be related to changes in mitochondrial function and protein clearance. [20] In this study, the systemic decrease in multiple antioxidants (such as plasma TAS, erythrocytes GSH, G6PD and erythrocyte antioxidant enzymes activities) with increase in marker of oxidative stress (MDA) provides evidence that peripheral indices of oxidative damage are elevated in AD/PD patients compared to controls.
G6PD is a key enzyme involved in the synthesis of NADPH, which is essential for keeping the normal level of reduced GSH; G6PD deficient erythrocytes are particularly sensitive to oxidative stress and reduction in G6PD activity may result in reduction of GSH level. [35] Both G6PD activity and GSH concentration are significantly reduced in AD and PD subjects compared to the controls in our study. This finding was in agreement with the finding of Sian et al., [36] on post-mortems studies, they reported that GSH levels in the SNpc of PD patients are remarkably lower than those of healthy subjects (60% compared to control subjects) while oxidized GSH (GSSG) levels are slightly increased. Although GSH is not the only antioxidant molecule reported to be altered in PD, it is hypothesized that the magnitude of its depletion is the earliest indicator of nigrostriatal degeneration. [37]
Gu et al., [38] on their study reported that GSH levels are depressed in AD cingulated cortex and AD substantia innominata, while Liu et al., [39] found these reduced levels only in red blood cells of male AD patients. However, increased GSH levels have been observed by Adams et al., [40] in the midbrain and in the caudate nucleus, while normal GSH contents was reported by Perry et al., [41] The dissenting results are most likely due to differences in techniques or difficulty in sample collection after death of AD patients. However, it has been observed that GSH protects cultured neurons against oxidative damage resulting from β-peptide and 4-hydroxynonenal (HNE), a lipid peroxidation product that is increased in AD. [42] This decrease in GSH may be due to its increased utilization to maintain a reduced cellular environment, which has been disturbed due to oxidative stress. Since GSH is a naturally occurring antioxidant, therefore it seems that much of it is being consumed in protecting the cell from cellular damage caused by cytotoxic radicals.
The SOD, CAT and GSH-Px are three primary enzymes, involved in direct elimination of active oxygen species (hydroxyl radical, superoxide radical, hydrogen peroxide) whereas GSH reductase, G6PD, and cytosolic GST are secondary enzymes, which help in the detoxification of reactive oxygen species (ROS) by decreasing peroxide levels or maintaining a steady supply of metabolic intermediates like GSH and NADPH necessary for optimum functioning of the primary antioxidant enzymes. [43] In the present study, a significant reduction in the activities of SOD, CAT, GSH-Px and G6PD with increase in MDA level of the erythrocytes for AD and PD patients was in line with an earlier report by other groups. [44],[45] The increase in the oxidative stress due to low activity of antioxidant enzymes might pave way for many secondary complications and may contribute to the neurodegeneration in AD and PD. SOD showed a significant reduction in activity in neurodegenerative disease patients, which may lead to an increase of superoxide radical. Zhang et al., [46] reported that some of the deleterious effects of N-methyl-4-phenyl-1, 2, 3, 6- tetrahydropyridine (MPTP) on striatal dopaminergic nerve terminals are mediated by both superoxide and hydroperoxides and they occur prior to dopaminergic neurodegeneration in the SN. Superoxide radicals can also react with nitric oxide to generate peroxynitrite (ONOO−), a putative neurotoxin. [47] A significant reduction in both CAT and GSH-Px activities in effect can increase the production of highly deleterious H 2 O 2 . Since SOD, CAT, GSH-Px and GSH are significantly reduced in AD and PD subjects in this study, TAS concentration follows suit. We also recorded a significant negative correlation between the SOD and the marker of oxidative stress (MDA); SOD is an enzyme that catalyzes the reaction of the superoxide radical (O 2−) to hydrogen peroxide and molecular oxygen (O 2 ). This antioxidant enzyme is found in the matrix of mitochondria which is the site of oxidative phosphorylation in neuronal cell. [24] However, no significant correlation was obtained between TAS and MDA. This can be attributed to the fact that other antioxidants such as the transition metal and the small molecule "sacrificial" antioxidants not assayed in this study may compensate for the reduction in other antioxidants in which all contribute to the systemic TAS.
| Conclusion | | |
Our study shows elevated oxidative stress and reduced activities of erythrocyte antioxidant enzymes such as SOD, GSH-Px and CAT. This revealed the possible role of free radicals in neurodegenerative diseases. Strong significant correlation between SOD and MDA shows that SOD reduction as result of increased free radical production contribute more to oxidative stress in mitochondria than other antioxidants, which may be responsible for the loss of cholinergic, noradrenergic and dopaminergic neurons that play a vital role in the pathogenesis of neurodegenerative diseases. Antioxidant therapy of SOD composition will be of immense benefit in neuronal mitochondria protection.
| References | | |
| 1. | McCord JM. The evolution of free radicals and oxidative stress Am J Med 2000;108:652-9. 
|
| 2. | Schipper HM. Redox neurology: Visions of an emerging subspecialty. Ann N Y Acad Sci 2004;1012:342-55.
[PUBMED] |
| 3. | Fang YZ, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition 2002;18:872-9.
|
| 4. | Wilson RS, Mccann JJ, Li Y, Aggarwal NT, Gilley DW, Evans DA. Nursing home placement, day care use, and cognitive decline in Alzheimer's disease. Am J Psychiatry 2007;164:910-5.
|
| 5. | Salmon DP, Thomas RG, Pay MM, Booth A, Hofstetter CR, Thai LJ, et al. Alzheimer's disease can be accurately diagnosed in very mildly impaired individuals. Neurology 2002;59:1022-8.
|
| 6. | Small GW. Brain-imaging surrogate markers for detection and prevention of age-related memory loss. J Mol Neurosci 2002;19:17-21.
[PUBMED] |
| 7. | Saido TC. Overview: A metabolism: from Alzheimer's research to brain aging control. In: Saido TC, editor. A Metabolism and Alzheimer's Disease. Georgetown, Texas: Landes Bioscience; 2003. p. 1-16.
|
| 8. | Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 2002;297:353-6.
|
| 9. | Ho GJ, Drego R, Hakimian E, Masliah E. Mechanisms of cell signaling and inflammation in Alzheimer's disease. Curr Drug Targets Inflamm Allergy 2005;4:247-56.
|
| 10. | Hynd MR, Scott HL, Dodd PR. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer's disease. Neurochem Int 2004;45:583-95.
|
| 11. | Tuppo EE, Arias HR. The role of inflammation in Alzheimer's disease. Int J Biochem Cell Biol 2005;37:289-305.
|
| 12. | Butterfield DA, Lauderback CM. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: Potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med 2002;32:1050-60.
|
| 13. | Szweda PA, Friguet B, Szweda LI. Proteolysis, free radicals, and aging. Free Radic Biol Med 2002;33:29-36.
|
| 14. | Keller JN, Hanni KB, Markesbery WR. Impaired proteasome function in Alzheimer's disease. J Neurochem 2000;75:436-9.
|
| 15. | Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein JB, Pierce WM, et al. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: Creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic Biol Med 2002;33:562-71.
|
| 16. | Ebadi M, Hiramatsu M. Glutathione and metallothionein in oxidative stress of Parkinson's disease. In: Poli G, Cadenas E, Packer L, editors. Free Radicals in Brain Pathophysiology. New York: Marcel Dekker; 2000. p. 427-65.
|
| 17. | Samii A, Nut JG, Ransom BR. Parkinson's disease. Lancet 2004;363:1783-93.
|
| 18. | Cookson MR. The biochemistry of Parkinson's disease. Annu Rev Biochem 2005;74:29-52.
|
| 19. | Wolters ECh, van Laar T, Berendse HW. Parkinsonism and related disorders. Amsterdam; VU University Press; 2007. p. 445-79.
|
| 20. | Zhou C, Huang Y, Przedborski S. Oxidative stress in Parkinson disease: A mechanism of pathogenic and therapeutic significance. Ann N Y Acad Sci 2008;1147:93-104.
|
| 21. | Seet RC, Lee CY, Lim EC, Tan JH, Quek AM, Chong WL, et al. Oxidative damage in Parkinson disease: Measurement using accurate biomarkers. Free Radical Biol Med 2010;48:560-6.
|
| 22. | Uttara1 B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 2009;7:65-74.
|
| 23. | Kidd PM. Parkinson's disease as multifactorial oxidative neurodegeneration: Implications for integrative management. Altern Med Rev 2000;5:502-29.
|
| 24. | Grisham MB, Jourd'Heuil D, Wink DA. Nitric Oxide I. Physiological chemistry of nitric oxide and its metabolites: Implications in inflammation. Am J Physiol 1999;276:G315-21.
|
| 25. | McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 1984;34:939-44.
|
| 26. | Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: A clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181-4.
|
| 27. | Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98.
|
| 28. | Beutler E, Duron O, Kelly BM. Improved methods for determination of blood glutathione. J Lab Clin Med 1968;61:882-8.
|
| 29. | Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 1990;186:421-31.
|
| 30. | McLemore JL, Beeley P, Thorton K, Morrisroe K, Blackwell W, Dasgupta A. Rapid automated determination of lipid hydroperoxide concentrations and total antioxidant status of serum samples from patients infected with HIV: Elevated lipid hydroperoxide concentrations and depleted total antioxidant capacity of serum samples. Am J Clin Pathol 1998;109:268-73.
|
| 31. | Paglia DE, Valentine WN. Studies on quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158-69.
|
| 32. | Woollians JA, Wiener G, Anderson PH, McMurray CH. Variation in the activities of glutathione peroxides and superoxide dismutase and in the concentration of copper in the blood in various breed crosses of sheep. Res Vet Sci 1983;34:253-6.
|
| 33. | Jain SK, McVie R. Hyperketonemia can increase lipid peroxidation and lower glutathione level in human erythrocytes in vitro and in type 1 diabetic patients. Diabetes 1999;48:1850-5.
|
| 34. | Johansson LH, Borg LA. A spectrophotometric method for determination of catalase activity in small tissue samples. Anal Biochem 1988;174:331-6.
|
| 35. | Jollow DJ, McMillan DC. Oxidative stress, glucose-6-phosphate dehydrogenase and the red cell. Adv Exp Med Biol 2001;500:595-605.
|
| 36. | Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, et al. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 1994;36:348-55.
|
| 37. | Garrido M, Tereshchenko Y, Zhevtsova Z, Taschenberger G, Bähr M, Kügler S. Glutathione depletioand overproduction both initiate degeneration of nigral dopaminergic neurons. Acta Neuropathol 2011;121:475-85.
|
| 38. | Gu M, Owen AD, Toffa SE, Cooper JM, Dexter DT, Jenner P, et al. Mitochondrial function, GSH and iron in neurodegeneration and Lewy body diseases. J Neurol Sci 1998;158:24-9.
|
| 39. | Liu H, Harrell LE, Shenvi S, Hagen T, Liu RM. Gender differences in glutathione metabolism in Alzheimer's disease. J Neurosci Res 2005;79:861-7.
|
| 40. | Adams JD Jr, Klaidman LK, Odunze IN, Shen HC, Miller CA. "Alzheimer's and Parkinson's disease. Brain levels of glutathione, glutathione disulfide, and vitamin E. Mol Chem Neuropathol 1991;14:213-26.
|
| 41. | Perry TL, Yong VW, Bergeron C, Hansen S, Jones K. Amino acids, glutathione, and glutathione transferase activity in the brains of patients with Alzheimer's disease. Ann Neurol 1987:21:331-6.
|
| 42. | Mark RJ, Lovell MA, Markesbery WR, Uchida K, Mattson MP. A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J Neurochem 1997;68:255-64.
|
| 43. | Singh RP, Khanna R, Kaw JL, Khanna SK, Das M. Comparative effect of benzanthrone and 3-bromobenzanthrone on hepatic xenobiotic metabolism and anti-oxidative defense system in guinea pigs. Arch Toxicol 2003;77:94-9.
|
| 44. | Marcus DL, Thomas C, Rodriguez C, Simberkoff K, Tsai JS, Strafaci JA, et al. Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer's disease. Exp Neurol 1998;150:40-4.
|
| 45. | Abraham S, Soundararajan CC, Vivekanandhan S, Behari M. Erythrocyte antioxidant enzymes in Parkinson's disease. Indian J Med Res 2005;121:111-5.
|
| 46. | Zhang J, Graham DG, Montine TJ, Ho YS. Enhanced N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice deficient in CuZn-superoxide dismutase or glutathione peroxidase. J Neuropathol Exp Neurol 2000;59:53-61.
|
| 47. | Beckman JS, Crow JP. Pathological implications of nitric oxide, superoxide and peroxinitrite formation. Biochem Soc Trans 1993;21:330-4.
|
[Figure 1]
[Table 1], [Table 2], [Table 3]
| This article has been cited by | | 1 |
Embryonic exposure to butylparaben and propylparaben induced developmental toxicity and triggered anxiety-like neurobehavioral response associated with oxidative stress and apoptosis in the head of zebrafish larvae |
|
| Christy Lite, Ajay Guru, Melita Juliet, Jesu Arockiaraj | | Environmental Toxicology. 2022; | | [Pubmed] | [DOI] | | | 2 |
The c-Abl/p73 pathway induces neurodegeneration in a Parkinson's disease model |
|
| Tamara Marín, Cristian Valls, Carolina Jerez, Tomas Huerta, Daniela Elgueta, René L. Vidal, Alejandra R. Alvarez, Gonzalo I. Cancino | | IBRO Neuroscience Reports. 2022; | | [Pubmed] | [DOI] | | | 3 |
Role of Endogenous Lipopolysaccharides in Neurological Disorders |
|
| Manjunath Kalyan, Ahmed Hediyal Tousif, Sharma Sonali, Chandrasekaran Vichitra, Tuladhar Sunanda, Sankar Simla Praveenraj, Bipul Ray, Vasavi Rakesh Gorantla, Wiramon Rungratanawanich, Arehally M. Mahalakshmi, M. Walid Qoronfleh, Tanya M. Monaghan, Byoung-Joon Song, Musthafa Mohamed Essa, Saravana Babu Chidambaram | | Cells. 2022; 11(24): 4038 | | [Pubmed] | [DOI] | | | 4 |
Investigation of anti-Parkinson activity of dicyclomine |
|
| Maham Sanawar,Uzma Saleem,Fareeha Anwar,Samra Nazir,Muhammad Furqan Akhtar,Bashir Ahmad,Tariq Ismail | | International Journal of Neuroscience. 2020; : 1 | | [Pubmed] | [DOI] | | | 5 |
Putative adjunct therapies to target mitochondrial dysfunction and oxidative stress in phenylketonuria, lysosomal storage disorders and peroxisomal disorders |
|
| Nadia Turton,Tricia Rutherford,Dick Thijssen,Iain P Hargreaves | | Expert Opinion on Orphan Drugs. 2020; : 1 | | [Pubmed] | [DOI] | | | 6 |
Neuroprotective effect of Reinwardtia indica against scopolamine induced memory-impairment in rat by attenuating oxidative stress |
|
| Prabhat Upadhyay,Rashmi Shukla,Kavindra Nath Tiwari,G. P. Dubey,Sunil Kumar Mishra | | Metabolic Brain Disease. 2020; | | [Pubmed] | [DOI] | | | 7 |
Effects of curcumin on mitochondria in neurodegenerative diseases |
|
| Hossein Bagheri,Faezeh Ghasemi,George E. Barreto,Rouhullah Rafiee,Thozhukat Sathyapalan,Amirhossein Sahebkar | | BioFactors. 2019; | | [Pubmed] | [DOI] | | | 8 |
Metabolomic investigations in cerebrospinal fluid of Parkinsonæs disease |
|
| Desiree Willkommen,Marianna Lucio,Franco Moritz,Sara Forcisi,Basem Kanawati,Kirill S. Smirnov,Michael Schroeter,Ali Sigaroudi,Philippe Schmitt-Kopplin,Bernhard Michalke,Anna Halama | | PLOS ONE. 2018; 13(12): e0208752 | | [Pubmed] | [DOI] | | | 9 |
Neuroprotective effect of a standardized extract of Centella asiatica ECa233 in rotenone-induced parkinsonism rats |
|
| Narudol Teerapattarakan,Hattaya Benya-aphikul,Rossarin Tansawat,Oraphan Wanakhachornkrai,Mayuree H. Tantisira,Ratchanee Rodsiri | | Phytomedicine. 2018; | | [Pubmed] | [DOI] | | | 10 |
Protective Effect of Antioxidants on Neuronal Dysfunction and Plasticity in Huntington’s Disease |
|
| Thirunavukkarasu Velusamy,Archana S. Panneerselvam,Meera Purushottam,Muthuswamy Anusuyadevi,Pramod Kumar Pal,Sanjeev Jain,Musthafa Mohamed Essa,Gilles J. Guillemin,Mahesh Kandasamy | | Oxidative Medicine and Cellular Longevity. 2017; 2017: 1 | | [Pubmed] | [DOI] | | | 11 |
Why should neuroscientists worry about iron? The emerging role of ferroptosis in the pathophysiology of neuroprogressive diseases |
|
| Gerwyn Morris,Michael Berk,André F. Carvalho,Michael Maes,Adam J. Walker,Basant K. Puri | | Behavioural Brain Research. 2017; | | [Pubmed] | [DOI] | | | 12 |
Oxidative and nitrosative stress in serum of patients with Parkinson’s disease |
|
| Hikmet Can Çubukçu,Mustafa Yurtdas,Zahide Esra Durak,Bilal Aytaç,Hafize Nalan Günes,Burcu Gökçe Çokal,Tahir Kurtulus Yoldas,Ilker Durak | | Neurological Sciences. 2016; | | [Pubmed] | [DOI] | |
|
 |
|
|
|
