Protective effect of Ginkgo biloba extract and pumpkin seed oil against neurotoxicity of rotenone in adult male rats

Journal of Applied Sciences Research

Volumn 5, Issue 6, 2009, Pages 622-635

  Ahmed, Hanaa H ^a,b   Abdel Rahman, Mona ^a,b   Ali, Rania S ^a,b   Moniem, Ahmed E Abdel ^a,b  

^a NATIONAL RESEARCH CENTRE   (Egypt)

^b Helwan University   (Egypt)

Author keywords

Dopamine; Ginkgo biloba extract; Neurotoxicity; Norepinepherine; Oxidative stress; Pumpkin seed oil; Rotenone

Indexed keywords

EID: 69049095353     PISSN: 1816157X     EISSN: 1819544X     Source Type: Journal    
DOI: None     Document Type: Article

References (102)

1. Ball, L.J. and S.J. Birge, 2002. Prevention of brain aging and dementia. Clin Geriatr Med., 18: 485-503.
2. Farooqui, T. and A.A. Farooqui, 2008. Aging: An Important Factor for the Pathogenesis of Neurodegenerative Diseases, Mechanisms of Ageing and Development, 129(11): 1-59.
3. Farooqui, A.A., 2009. Hot Topics in Neural Membrane Lipidology Springer, New York.
4. Doherty, J.D., 2006. Screening pesticides for neuropa thogenicity. J Biomedicine and Biotechnology, 1-13.
5. Dawson, T.M. and V.L. Dawson, 2003. Molecular pathways of neurogeneration in Parkinson's Disease. Science, 302: 819-922.
6. Bashkatova, V., M. Alam, A. Vanin and W.J. Schmidt, 2004. Chronic administration of rotenone increases levels of nitric oxide and lipid peroxidation products in rat brain. Exp. Neurol., 186: 235-241.
7. Beal, M.F., 2001. Experimental models of Parkinson's disease. Nat Rev Neurosci., 2: 325-334.
8. Schmidt, N. and B. Ferger, 2001. Neurochemical findings in the MPTP model of Parkinson's disease. J Neural Transm, 108: 1263-1282.
9. Betarbet, R., T.B. Sherer, G. MacKenzie, M. Garcia-Osuna, A.V. Panov and T.J. Greenamyre, 2000. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci, 3: 1301-1306.
10. Greenamyre, J.T., T.B. Sherer, R. Betarbet and A.V. Panov, 2001. Complex I and Parkinson's disease. IUBMB Life, 52: 135-141.
11. Sherer, T.B., J.H. Kim, R. Betarbet and J.T. Greenamyre, 2003. Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol., 179: 9-16.
12. Hirsch, A., G. Hoglinger, E. Rousselet, T. Breidert, K. Parain, J. Feger, M. Ruberg, A. Prigent, C. Cohen-Salmon and J.M. Launay, 2003. Animal models of Parkinson's disease in rodents induced by toxins: an update. J Neural Transm Suppl., 89-100.
13. Ahmadi, F.A., D.A. Linseman, T.N. Grammatopoulos, S.M. Jones, R.J. Bouchard, C.R. Freed, K.A. Heidenreich and W.M. Zawada, 2003. The pesticide rotenone induces caspase-3-mediated apoptosis in ventral mesencephalic dopaminergic neurons. J Neurochem., 87: 914-921.
14. Kweon, G.R., J.D. Marks, R. Krencik, E.H. Leung, P.T. Schumacker, K. Hylandl and U.J. Kang, 2004. Distinct mechanisms of neurodegeneration induced by chronic complex I inhibition in dopaminergic and non-dopaminergic cells, J Biol Chem., 279: 51783-51792.
15. Moon, Y., K.H. Lee, J.H. Park, D. Geum and K. Kim, 2005. Mitochondrial membrane depolarisation and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10. J. Neurochem., 93: 1199-1208.
16. Radad, K., W.D. Wolf-Dieter Rausch and G. Gille, 2006. Rotenone induces cell death in primary dopaminergic culture by increasing ROS production and inhibiting mitochondrial respiration. Neurochemistry International, 49(4): 379-386.
17. Zhang, Y., V.L. Dawson and T.M. Dawson, 2000. Oxidative stress and genetics in the pathogenesis of Parkinson's disease. Neurobiol Dis, 7: 240-250.
18. Dexter, D.T., C.J. Carter, F.R. Wells, F. Javoy-Agid, Y.A. Agid, A. Lees, P. Jenner and C.D. Marsden, 1989. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J Neurochem., 52: 381-389.
19. Jenner, P., 1991. Oxidative stress as a cause of Parkinson's disease. Acta Neurol Scand, 84: 6-15.
20. Sanchez-Ramos, J.R., E. Övervik and B.N. Ames, 1994. A marker of oxyradical-mediated DNA damage (8-hydroxy-2 deoxyguanosine) is increased in the nigro-striatum of Parkinson's disease brain. Neurodegeneration, 3: 197-204.
21. Zhang, J., G. Perry, M.A. Smith, D. Robertson, S.J. Olson, D.G. Graham and T.J. Montine, 1999. Parkinson's disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol., 154: 1423-1429.
22. Floor, E. and M.G. Wetzel, 1998. Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortexmeasured with an improved dinitrophenylhydrazine assay. J Neurochem., 70: 268-275.
23. Sian, J., D.T. Dexter, A.J. Lees, S.E. Daniel, Y.A. Agid, F. Javoy-Agid, P. Jenner and C.D. Marsden, 1994. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann. Neurol., 36: 348-355.
24. Hladovec, J., 1977. Antithrombotic effects of some flavonoids alone and combined with acetylsalicylic acid. Arzneimittelforschung, 27: 1989-1992.
25. Ahlemeyer, B. and J. Krieglstein, 2003. Neuroprotective effects of Ginkgo biloba extract. Cell Mol. Life Sci., 60: 1779-1792.
26. Ahmad, M. S. Saleem, A.S. Ahmad, S. Yousuf, M.A. Ansari, M.B. Khan, T. Ishrat, R.K. Chaturvedi, A.K. Agrawal and F. Islam, 2005. Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced Parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemical evidences. J Neurochemistry, 93: 94-104.
27. O'Brien, J., P. Desmond, D. Ames, I. Schweitzer, S. Harrigan and B. Tress, 1996. A magnetic resonance imaging study of white matter lesions in depression and Alzheimer's disease. Br. J. Psychiatry, 168: 477-485.
28. Klein, J., S.S. Chatterjee and K. Loffelholz, 1997. Phospholipid breakdown and choline release under hypoxic conditions: inhibition by bilobalide, a constituent of Ginkgo biloba. Brain Res., 755: 347-350.
29. Chandrasekaran, K., Z. Mehrabian, B. Spinnewyn, C. Chinopoulos, K. Drieu and G. Fiskum, 2003. Neuroprotective effects of bilobalide, a component of Ginkgo biloba extract (EGb 761) in global brain ischemia and in excitotoxicity-induced neuronal death. Pharmacopsychiatry, 36: S89-S94.
30. Sloley, B.D., L.J. Urichuk, P. Morley, J. Durkin, J.J. Shan, P.K.T. Pang and R.T. Coutts, 2000. Identification of Kaempferol as a monoamine oxidase inhibitor and potential neuroprotectant in extracts of Ginkgo biloba leaves. J. Pharm. Pharmacol., 52: 451-469.
31. Smith, J.V., A.J. Burdick, P. Golik, I. Khan, D. Wallace and Y. Luo, 2002. Anti-apoptotic properties of Ginkgo biloba extract EGb 761 in differentiated PC12 cells. Cell Mol Biol., (Noisyle-grand), 48: 699-707.
32. Bastianetto, S. and R. Quirion, 2002. Natural extracts as possible protective agents of brain aging. Neurobiol Aging, 23: 891-897.
33. Yang, S.F., Q. Wu, A.S. Sun, X.N. Huang and J.S. Shi, 2001. Protective effect and mechanism of Ginkgo biloba leaf extracts for Parkinson disease induced by 1-methyl 1-4-phenyl-1,2,3,6-tetrahydropyridine. Acta Pharmacol Sin., 22: 1089-1093.
34. Al-Zuhair, H., A.A. Abdel Fattah and M. Ibrahim, 2000. Pumpkin-seed oil modulates the effect of felodipine and captopril in spontaneously hypertensive rats. Pharmacological Research, 41(5): 555-563.
35. Woodward, W.R., C.W. Olanow, R.M. Beckner, R.A. Hauser, L.L. Gauger, J.M. Cedarbaum and J.G. Nutt, 1993. The effect of L-dopa infusions with and without phenylalanine challenges in parkinsonian patients: Plasma and ventricular CSF L-dopa levels and clinical responses. Neurol., 43: 1704-1708.
36. Murkovic, M., V. Piironen, A.M. Lampi, T. Kraushofer and G. Sontag, 2004. Changes in chemical composition of pumpkin seeds during the roasting process for production of pumpkin seed oil (Part 1: non-volatile compounds). Food Chemistry, 84: 359-365.
37. Ryan, E., K. Galvin, T.P. O'Connor, A.R. Maguire and N.M. O'Brien, 2007. Phytosterol, squalene, tocopherol content and fatty acid profile of selected seeds, grains, and legumes. Plant Foods Hum Nutr., 62: 85-91.
38. Fujikawa, T., N. Kanada, A. Shimada, M. Ogata, I. Suzuki, I. Hayashi and K. Nakashima, 2005. Effect of sesamin in Acanthopanax senticosus harms on behavioral dysfunction in rotenone-induced parkinsonian rats. Biol Pharm Bull., 28(1): 169-172.
39. Inden, M., Y. Kitamura, H. Takeuchi, T. Yanagida, K. Takata, Y. Kobayashi, T. Taniguchi, K. Yoshimoto, M. Kaneko, Y. Okuma, T. Taira, H. Ariga and S. Shimohama, 2007. Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone. J Neurochemistry, 101: 1491-1504.
40. Glowinski, J. and L.L. Iversen, 1966. Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem., 13(8): 655-669.
41. 2+-ATPase activities induced by the in vitro galactosaemia. Pharmacological Research, 49: 475-479.
42. th edn. Oxford University Press, Oxford New York Toronto, 188-189, 237-240, 290-291.
43. Koracevic, D., G. Koracevic, V. Djordjevic, S. Andrejevic and V. Cosic, 2001. Method for the measurement of antioxidant activity in human fluids. J Clin Pathol., 54(5): 356-361.
44. Berkels, R., S. Purol-Schnabel and R. Roesen, 2004. Measurment of nitric oxide by reconversion of nitrate/nitrite to NO. J Humman Press., 279: 1-8.
45. Ellman, G.L., 1959. Tissue Sulfhydryl groups. Arch Biochem Biophys., 74: 214-218.
46. Satoh K., 1978. Plasma lipid peroxide in cerebrovascular disorder determined by a new colorimetric method. Clinica Chimica Acta, 90: 37-43.
47. Joshi, U.M., H.P. Shah, and S.P. Sudhama, 1979. A. sensitive and specific enzyme immunoassay for serum testosterone. Steroids, 34(1): 35-46.
48. Chang, C.C., 1964. A senestive method for spectrofluorometric assay of chatecholamines. Int J Neuropharmacol., 4: 643-649.
49. Ciarlone, A.E., 1978. Further modification of a fluoromertric method for analyzing brain amines. Microchem J., 23: 9-12.
50. Di Monte, D.A., 2003. The environment and Parkinson's disease: is the nigrostriatal system preferentially targeted by neurotoxins? The Lancet Neurology, 2: 531-538.
51. Hirata, Y. and T. Nagatsu, 2005. Rotenone and CCCP inhibit tyrosine hydroxylation in rat striatal tissue slices. Toxicology, 216: 9-14.
52. Ren, Y., W. Liu, H. Jiang, Q. Jiang and J. Feng, 2005. Selective vulnerability of dopaminergic neurons to microtubule depolymerization, J Biol Chem., 280: 34105-34112.
53. Antkiewicz-Michaluk, L., B. Karolewicz, I. Romanska, J. Michaluk, A. Bojarski and J. Vetulani, 2003. 1-Methyl-1,2,3,4-tetrahydroisoquinoline protects against rotenoneinduced mortality and biochemical changes in rat brain. Eur J Pharmacol., 466: 263-269.
54. Sloley, B.D., P. Morlev, J. Durkin, J.J. Shan, P.K. Pang and R.T. Coutts, 2000. Identification of kaempferol as a monoamine oxidase inhibitor and potential neuroprotectant in extracts of Ginkgo biloba leaves, J Pharm Pharmacol., 52: 451-459.
55. Yeh, K.Y., H.F. Pu, K. Kaphle, S.F. Lin, L.S. Wu, J.H. Lin and Y.F. Tsai, 2008. Ginkgo biloba extract enhances male copulatory behavior and reduces serum prolactin levels in rats. Hormones and Behavior, 53(1): 225-231.
56. Adachi, K., M. Izumi and T. Mitsuma, 1999. Effect of vitamin E deficiency on rat brain monoamine metabolism. Neurochemical Research, 24(10): 1307-1311.
57. Meng, H., C. Li, L. Feng, B. Cheng, F. Wu, X. Wang, Z. Li and S. Liu, 2007. Effects of Ginkgolide B on 6-OHDA-induced apoptosis and calcium over load in cultured PC12. Int J Devl Neuroscience, 25: 509-514.
58. Eckert, A., U. Keil, I. Scherping, S. Hauptmann and W.E. Müller, 2005. Stabilization of mitochondrial membrane potential and improvement of neuronal energy metabolism by Ginkgo biloba extract EGb 761. Ann NY Acad Sci., 1056: 474-485.
59. Chen, J.X., H. Zeng, X. Chen, C.Y. Su and C.C. Lai, 2001. Induction of heme oxygenase-1 by ginkgo biloba extract but not its terpenoids partially mediated its protective effect against lysophosp h a tidylc h o lin e -induced damage. Pharmacological Research, 43(1): 63-69.
60. Chandrasekaran, K., Z. Mehrabian, B. Spinnewyn, K. Drieu and G. Fiskumn, 2001. Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia. Brain Research, 922: 282-292.
61. Roghani, M. and G. Behzadi, 2001. Neuroprotective effect of vitamin E on the early model of Parkinson's disease in rat: behavioral and histochemical evidence. Brain Research, 892: 211-217.
62. Schapira, A.H., 1999. Mitochondrial involvement in Parkinson's disease, Huntington's disease, hereditary spastic paraplegia and Friedreich's ataxia. Biochim Biophys Acta, 1410: 159-170.
63. Parker, Jr W.D., S.J. Boyson and J.K. Parks, 1989. Abnormalities of the electron transport chain in idiopathic Parkinson's disease. Ann Neurol., 26: 719-723.
64. Zhang, Y., O. Marcillat, C. Giulivi, L. Ernster and K.J. Davies, 1990. The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J Biol Chem., 265: 16330-16336.
65. Dauer, W. and S. Przedborski, 2003. Parkinson's disease: mechanisms and models. Neuron, 39: 889-909.
66. Dexter, D.T., C.J. Carter, F.R. Wells, F. Javoy-Agid, Y.A. Agid, A. Lees, P. Jenner and C.D. Marsden, 1989. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J Neurochem., 52: 381-389.
67. Good, P.F., C.W. Olanow and D.P. Perl, 1992. Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson's disease: a LAMMA study. Brain Res., 593:343-346.
68. Gutteridge, J.M.C., 1982. Free radicals damage to lipids, amino acids, carbohydrates and nucleic acids, determined by TBA reactivity. Int J Biochem., 14: 649-654.
69. Jenner, P., D.T. Dexter, J. Sian, A.H. Schapira and C.D. Marsden, 1992. Oxidative stress as a cause of nigral cell death in Parkinson's disease and incidental Lewy body disease. The royal kings and queens Parkinson's disease research group. Ann Neurol., 32: S82-87.
70. Flanagen, R.J. and T.J. Meredith, 1993. Use of Nacetylcysteine in clinical toxicology. Am J Med., 91(3C):131S-139S.
71. Sharma, A., P. Kaur, B. Kumar, S. Prabhakar and K.D. Gill, 2008. Plasma lipid peroxidation and antioxidant status of Parkinson's disease patients in the Indian population. Parkinsonism and Related Disorders, 14: 52-57.
72. Al-Zuhair, H., A.A. Abdel Fattah and M. Ibrahim, 2000. Pumpkin-seed oil modulates the effect of felodipine and captopril in spontaneously hypertensive rats. Pharmacological Research, 41(5): 555-563.
73. Fahim, A.T., A.A. Abdel Fattah, A.M. Agha and M.Z. Gad, 1995. Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats. Pharmacological Research, 31(I): 73-79.
74. Al-Zuhair, H., A.A. Abdel Fattah and H.A. Latif, 1997. Efficacy of simvastatin and pumpkin-seed oil in the management of dietary-induced hypercholesterolemia. Pharmacol Res., 35: 403-408.
75. Bashkatova, V., M. Alam, A. Vanin and W.J. Schmidt, 2004. Chronic administration of rotenone increases levels of nitric oxide and lipid peroxidation products in rat brain. Exp Neurol., 186(2): 235-241.
76. Li, J., M.L. Spletter, D.A. Johnson, L.S. Wright, C.N. Svendsen and J.A. Johnson, 2005. Rotenoneinduced caspase 9/3-independent and -dependent cell death in undifferentiated and differentiated human neural stem cells. J Neurochemistry, 10(1111): 1471-4159.
77. Testa, C.M., T.B. Sherer and T. Greenamyre, 2005. Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Molecular Brain Research, 134: 109-118.
78. McGeer, P.L., S. Itagaki, B.E. Boyes and E.G. McGeer, 1988. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology, 38: 1285-1291.
79. Hunot, S., F. Boissiere, B. Faucheux, B. Brugg, A. Mouatt-Prigent, Y. Agid and E.C. Hirsch, 1996. Nitric oxide synthase and neuronal vulnerability in Parkinson's disease. Neuroscience, 72: 355-363.
80. Drechsel, D.A., and M. Patel, 2008. Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson's disease. Free Radic Biol Med., 44(11):1873-1886.
81. Calapai, G., A. Crupi, F. Firenzuoli, M.C. Marciano, F. Squadrito, G. Inferrera, A. Parisi, A. Rizzo, C. Crisafulli, A. Fiore and A.P. Caputi, 2000. Neuroprotective effects of Ginkgo biloba extract in brain ischemia are mediated by inhibition of nitric oxide synthesis. Life Sci., 67: 2673-2683.
82. Shen, J., J. Wang, B. Zhao, J. Hou, T. Gao and W. Xin, 1998. Effects of EGb 761 on nitric oxide and oxygen free radicals, myocardial damage and arrythmia in ischemia-reperfusion injury in vivo. Biochem. Biophys. Acta., 1406: 228-236.
83. Sharma, H.S., K. Drieu, P. Alm and J. Westman, 2000. Role of nitric oxide in blood-brain barrier permeability, brain edema and cell damage following hyperthermic brain injury. An experimental study using EGB-761 and Ginkgolide B pretreatment in the rat. Acta Neurochir. Suppl., 76: 81-86.
84. Du, Z.Y. and X.Y. Li, 1998. Effects of ginkgolides on interleukin-1, tumor necrosis factor-a and nitric oxide production by rat microglia stimulated with lipolpolysaccharides in vitro. Arzneimittelforschung/Drug Res., 48: 1126-1130.
85. Wadsworth, T.L. and D.R. Koop, 2001. Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide. Chem Biol Interact, 137: 43-58.
86. Seyfried, J., F. Soldner, W.S. Kunz, J.B. Schulz, T. Klockgether, K.A. Kovar and U. Wullner, 2000. Effect of 1-methyl-4-phenylpyridinium on glutathione in rat pheochromocytoma PC 12 cells. Neurochem Int., 36: 489-497.
87. Sherer, T.B., R. Betarbet and J.T. Greenamyre, 2002. Environment, mitochondria, and Parkinson's disease. Neuroscientist, 8: 192-197.
88. Krzywanski, D.M., D.A. Dickinson, K.E. Iles, A.F. Wigley and C.C. Franklin, 2004. Variable regulation of glutamate cysteine ligase subunit proteins affects glutathione biosynthesis in response to oxidative stress. Arch Biochem Biophys., 423(1): 116-125.
89. Sasaki, K., S. Hatta, K. Wada, N. Ueda, T. Yoshimura, T. Endo, M. Sakata, T. Tanaka and M. Haga, 2002. Effects of extract of Ginkgo biloba leaves and its constituents on carcinogenmetabolizing enzyme activities and glutathione levels in mouse liver. Life Sci., 70: 1657-1667.
90. Rimbach, G., K. Gohil, S. Matsugo, H. Moini, C. Saliou, F. Virgili, S.U. Weber and L. Packer, 2001. Induction of glutathione synthesis in human keratinocytes by Ginkgo biloba extract (EGb 761). Biofactors, 15: 39-52.
91. Dreikorn, K., R. Berges, L. Pientka and U. Jonas, 2002. Phytotherapy of benign prostatic hyperplasia. Current evidence-based evaluation. Urologe A., 41(5): 447-451.
92. Abdel-Rahman, M.K. 2006. Effect of pumpkin seed (Cucurbita pepo L.) diets on benign prostatic hyperplasia (BPH): Chemical and morphometric evaluation in rats. World Journal of Chemistry, 1(1): 33-40.
93. Li, N., K. Ragheb, G. Lawler, J. Sturgis, B. Rajwa, J.A. Melendez and J.P. Robinson, 2003. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem., 278: 8516-8525.
94. Sherer, T.B., R. Betarbet, C.M. Testa, B.B. Seo, J.R. Richardson, J.H. Kim, G.W. Miller, T. Yagi, A. Matsuno-Yagi and J.T. Greenamyre, 2003. Mechanism of toxicity in rotenone models of Parkinson's disease. J Neuroscience, 23(34):10756 -10764.
95. Nicolson, G.L., 2007. Metabolic syndrome and mitochondrial function: molecular replacement and antioxidant supplements to prevent membrane peroxidation and restore mitochondrial function. J Cell Biochem., 15; 100(6):1352-1369.
96. Alam, M. and W.J. Schmidt, 2004. l-DOPA reverses the hypokinetic behaviour and rigidity in rotenone-treated rats. Behav Brain Res., 153: 439-446.
97. Chen, Y.C., M.L. Nagpal, D.M. Stocco and T. Lin, 2007. Effects of genistein, resveratrol and quercetin on steroidogenesis and proliferation of MA-10 mouse Leydig tumor cells. J. Endocrinol., 192: 527-537.
98. Prasad, A.S., C.S. Mantzoros, F.W. Beck, J.W. Hess and G.J. Brewer, 1996. Zinc status and serum testosterone levels of healthy adults. Nutrition, 12: 344-348.
99. Greenamyre, J.T. and T.G. Hastings, 2004. Parkinson's-divergent causes, convergent mechanisms. Science, 304: 1120-1122.
100. Souza, J.M., B.I. Giasson, Q. Chen, V.M.Y. Lee and H. Ischiropoulos, 2000. Dityrosine cross-linking promotes formation of stable á-synuclein polymers. J Biol Chem., 275: 18344-18349.
101. Hoglinger, G.U., J. Feger, A. Prigent, P.P. Michel, K. Parain, P. Champy, M. Ruberg, W.H. Oertel and E.C. Hirsch, 2003. Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J Neurochem., 84: 491-502.
102. Giasson, B.I., J.E. Duda, I.V. Murray, Q. Chen, J.M. Souza, H.I. Hurtig, H. Ischiropoulos, J.Q. Trojanowski and V.M. Lee, 2000. Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science, 290: 985-989.