Abstract
EGb761 has been suggested to be an antioxidant and free radical scavenger. Excess generation of free radicals, leading to lipid peroxidation (LP), has been proposed to play a role in the damage to striatal neurons induced by 1-methyl-4-phenylpyridinium (MPP+). We investigated the effects of EGb761 pretreatment on MPP+ neurotoxicity. C-57 black mice were pretreated with EGb761 for 17 days at different doses (0.63, 1.25, 2.5, 5 or 10 mg/kg) followed by administration of MPP+, (0.18, 0.36 or 0.72 mg/kg). LP was analyzed in corpus striatum at 30 min, 1 h, 2 h and 24 h after MPP+ administration. Striatal dopamine content was analyzed by HPLC at the highest EGb761 dose at 2 h and 24 h after MPP+ administration. MPP+-induced LP was blocked (100%) by EGb761 (10 mg/kg). Pretreatment with EGb761 partially prevented (32%) the dopamine-depleting effect of MPP+ at 24 h. These results suggest that supplements of EGb761 may be effective at preventing MPP+-induced oxidative stress.
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REFERENCES
Jenner, P. 1989. Clues to the mechanism underlying dopamine cell death in Parkinson's disease. J. Neurol. Neurosurg. Psychiatry (suppl):22–28.
Javoid-Agid F., Ruberg, M., Hirsch, E., Cash, R., Raisman, R., Taquet, H., Epelbaum, J., Scatton, B., Duyckaerts, C., and Agid, Y. 1986. Recent progress in the neurochemistry of Parkinson's disease. Pages 67–83, in Recent Developments in Parkinson's disease. Raven Press, New York.
Reiter, R. J. 1995. Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J. 9:526–533.
Halliwel, B. 1992. Oxygen radicals as key mediators in neurological disease: fact or fiction? Ann. Neurol. 32:S10–S15.
Niki, E., Noguchi, N., and Gotoh, N. 1993. Dynamics of lipid peroxidation and its inhibition by antioxidants. Biochem. Soc. Trans. 21:313–317.
Youdim, M. B. H., Schachar, D. Ben., and Riederer, P. 1989. Is Parkinson's disease a progressive siderosis of substantia nigra resulting in increased iron and melanin induced neurodegeneration? Acta Neurol. Scand. 126:47–54.
Sian, J., Dexter, D. T., Lees, A. J., Daniel, S., Agid, Y., Javoy-Agid, F., Jenner, P. P., and Marsden, C. D. 1994. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting the basal ganglia. Ann. Neurol. 36:348–355.
Dexter, D. T., Carter, C. J., Wells, F. R., Javoy-Agid, F., Agid, Y., Lees, A., Jenner, P., and Marsden, C. D. 1989. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J. Neurochem. 52:381–389.
Quinn, N. P. 1990. Levodopa-based therapy. Pages 169–184, in Therapy of Parkinson's Disease. Marcel Dekker, New York.
Kanazawa, I. 1986. Clinical pathophysiology of basal ganglia diseases. Vol. 49, pages 65–92, in Vinken, P. T., Bruyn, G. W., Klawans, H. L. (eds): Handbook of Clinical Neurology. Elsevier Science Publishers, New York.
Gerlach, M., Riederer, P., Przuntek, H., and Youdim, M. B. H. 1991. MPTP mechanisms of neurotoxicity and their implications for Parkinson's disease. Eur. J. Pharmacol. Mol. Pharmacol. 208:273–286.
Javitch, J. A., D'Amato, R. J., Strittmatter, S. M., and Snyder, S. H. 1985. Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine: Uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc. Natl. Acad. Sci. USA 82:2173–2177.
Nicklas, W. J., Vyas, I., and Heikkila, R. E. 1985. Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenylpyridinium, a metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Life Sci. 36:2503–2508.
Chan, P., DeLanney, L. E., Irwin, I., Langston, J. W., and DiMonte, D. 1991. Rapid ATP loss caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mouse. J. Neurochem. 57:348–351.
Zang, L. Y. and Misra, H. P. 1993. Generation of reactive oxygen species during the monoamine oxidase-catalyzed oxidation of the neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J. Biol. Chem. 268:16504–16512.
Adams, J. D., Klaidman, L. K., and Leung, A. 1993. MPP+ and MPDP+ induced oxygen radical formation with mitochondrial enzymes. Free Radic. Biol. Med. 15:181–186.
Zhang, Y., Marcillat, O., Giulivi, C., Ernster, L., and Davies, K. J. 1990. The oxidative inactivation of mitochondrial eletron transport chain components and ATPase. J. Biol. Chem. 265:16330–16336.
Adams, J. D. and Odunze, I. N. 1991. Biochemical mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity. Biochem. Pharmacol. 41:1099–1105.
Yurek, D. M., Deutch, A. Y., Roth, R. H., and Sladek, J. R. Jr. 1989. Morphological, neurochemical, and behavioral characterizations associated with the combined treatment of diethyldithiocarbamate and 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine in mice. Brain Res. 497:250–259.
Przedborski, S., Kostic, V., Jackson-Lewis, V., Naini, A. B., Simonetti, S., Fahn, S., Carlson, E., Epstein, C. J., and Cadet, J. L. 1992. Transgenic mice with increased Cu/Zn-superoxide dismutase activity are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. J. Neurosci. 12:1658–1667.
Rojas, P. and Ríos, C. 1993. Increased striatal lipid peroxidation after intracerebroventricular MPP+ administration to mice. Pharmacol. Toxicol. 72:364–368.
Ríos, C., Alvarez-Vega, R., and Rojas, P. 1995. Depletion of copper and manganese in brain after MPTP treatment of mice. Pharmacol. Toxicol. 76:348–352.
Rojas, P. and Ríos, C. 1995. Short-term manganese pretreatment partially protects against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine neurotoxicity. Neurochem. Res. 20:1217–1223.
Alcaraz-Zubeldia, M., Rojas, P., Boll, C., and Ríos, C. 2001. Neuroprotective effect of acute and chronic administration of copper (II) sulfate against MPP+ neurotoxicity in mice. Neurochem. Res. 26:59–64.
DeFeudis, F. V. 1998. Ginkgo biloba extract (EGb761): from Chemistry to the Clinic. Pages 401. Ullstein Medical, Wiesbaden.
Marcocci, L., Packer, L., Droy-Lefaix, M., Sekaki, A., and Gardes-Albert, M. 1994. Antioxidant action of Ginkgo biloba extract EGb761. Methods Enzymol. 234:462–475.
Marcocci, L., Maguire, J. J., Droy-Lefaix, M. T., and Packer, L. 1994. The nitric oxide-scavenging properties of Ginkgo biloba extract EGb761. Biochem. Biophys. Res. Commun. 201:748–755.
Kobuchi, H., Droy-Lefaix, M. T., Christen, Y., and Packer, L. 1997. Ginkgo biloba extract (EGb761): Inhibitory effect on nitric oxide production in the macrophage cell line RAW 264.7. Biochem. Pharmacol. 53:897–903.
Ramassamy, C., Clostre, F., Christen, Y., and Costentin, J. 1990. Prevention by a Ginkgo biloba extract (GBE 761) of the dopaminergic neurotoxicity of MPTP. J. Pharm. Pharmacol. 42:785–789.
Brailowsky, S. and Montiel, T. 1997. Motor function in young and aged hemiplegic rats: effects of a Ginkgo biloba extract. Neurobiol. Aging 18:219–227.
Mihatsch, W., Russ, H., and Przuntek, H. 1988. Intracerebroventricular administration of MPP+ in mice: Effects of simultaneously administered nomifensine, deprenyl and 1-t-butyl-4,4-diphenylpiperidine. J. Neural. Transm. 71:177–188.
Glowinski, J. and Iversen, L. L. 1966. Regional studies of catecholamines in the rat brain. Disposition of 3H-Norepinephrine, 3H-dopamine and 3H-DOPA in various regions of the brain. J. Neurochem. 13:655–669.
Triggs, W. J. and Willmore, L. J. 1984. In vivo lipid peroxidation in rat brain following intracortical Fe2+ injection. J. Neurochem. 42:976–979.
Maitra, I., Marcocci, L., Droy-Lefaix, M. T., and Packer, L. 1995. Peroxyl Radical scavenging activity of Ginkgo biloba extract EGb761. Biochem. Pharmacol. 49:1649–1655.
Sloley, B. D., Urichuk, L. J., Morley, P., Durkin, J., Shan, J. J., Pang, P. K. T., and Coutts, R. T. 2000. Identification of kaempferol as a monoamine oxidase inhibitor and potential neuroprotectant in extracts of Ginkgo biloba leaves. J. Pharm. Pharmacol. 52:451–459.
Ni, Y., Zhao, B., Hou, J., and Xin, W. 1996. Preventive effect of Ginkgo biloba extract on apoptosis in rat cerebellar neuronal cells induced by hydroxyl radicals. Neurosc. Lett. 214:115–118.
Ramassamy, C., Girbe, F., Christen, Y., and Costentin, J. 1993. Ginkgo biloba extract EGb761 or trolox C prevent the ascorbic acid/Fe2+ induced decrease in synaptosomal membrane fluidity. Free Radic. Res. Commun. 19:341–350.
Sastre, J., Millán, A., García, J., Plá, R., Juan, G., Pallardó, F. V., O'Connor, E., Martín, J. A., Droy-Lefaix, M. T., and Viña, J. 1998. A ginkgo biloba extract (EGb761) prevents mitochondrial aging by protecting against oxidative strees. Free Radic. Biol. Med. 24:298–304.
Oyama, Y., Chikahisa, L., Ueha, T., Kanemaru, K., and Noda, K. 1996. Ginkgo biloba extract protects brain neurons against oxidative strees induced by hydrogen peroxide. Brain Res. 712:349–352.
Dorman, D. C., Coté, L. M., and Buck, W. B. 1992. Effects of an extract of Ginkgo biloba on bromethalin-induced cerebral lipid peroxidation and edema in rats. Am. J. Vet. Res. 53:138–142.
Bors, W., Heller, W., Michel, C., and Saran, M. 1990. Flavonoids as antioxidants: Determination of radical-scavenging efficiencies. Methods Enzymol. 186:343–355.
Afanas'ev, I. B., Dorozhko, A. I., Brodskii, A. V., Kostyuk, V. A., and Potapovitch, A. I. 1989. Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation. Biochem. Pharmacol. 38:1763–1769.
Havsteen, B. 1983. Flavonoids, a class of natural high pharmacological potency. Biochem. Pharmacol. 32:1141–1148.
Joyeux, M., Lobstein, A., Anton, R., and Mortier, F. 1995. Comparative antilipoperoxidant, antinecrotic and scavenging properties of terpenes and biflavones from Ginkgo and some flavonoids. Planta. Med. 61:126–129.
Zaleska, M. M., Nagy, K., and Floyd, R. A. 1989. Iron-induced lipid peroxidation and inhibition of dopamine synthesis in striatum synaptosomes. Neurochem. Res. 14:597–605.
Rafalowska, U., Liu, G. J., and Floyd, R. A. 1989. Peroxidation induced changes in synaptosomal transport of dopamine and gama-aminobutyric acid. Free Radical Biol. Med. 6:485–492.
Ramassamy, C., Naudin, B., Christen, Y., Clostre, F., and Costentin, J. 1992. Prevention by Ginkgo biloba extract (EGb761) and trolox C of the decrease in synaptosomal dopamine or serotonin uptake following incubation. Biochem. Pharmacol. 44:2395–2401.
Moreau, J-P., Eck, J., McCabe, J., and Skinner, S. 1986. Absorption, distribution et élimination de léxtrait marqué de Ginkgo biloba chez le rat. Presse Méd. 4:2401–2402.
Wu, Wei-Ran and Zhu, Xing-Zu. 1999. Involvement of monoamine oxidase inhibition in neuroprotective and restorative effects of Ginkgo biloba extract against MPTP-induced nigrostriatal dopaminergic toxicity in C-57 mice. Life Sci. 65:157–164.
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Rojas, P., Garduño, B., Rojas, C. et al. EGb761 Blocks MPP+-Induced Lipid Peroxidation in Mouse Corpus Striatum. Neurochem Res 26, 1245–1251 (2001). https://doi.org/10.1023/A:1013971524150
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DOI: https://doi.org/10.1023/A:1013971524150