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Impact of Ginkgo Biloba Extract EGb 761 on Ischemia/Reperfusion – Induced Oxidative Stress Products Formation in Rat Forebrain

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Abstract

Dysbalance in reactive oxygen/nitrogen species is involved in the pathogenesis of cerebral ischemia/reperfusion injury (IRI). Ginkgo biloba extract (Egb 761) pre-treatment was used to observe potential antioxidant/neuroprotective effect after global ischemia/reperfusion. Egb 761 significantly decreased the level of lipoperoxidation (LPO) in rat forebrain total membrane fraction (homogenate) induced by in vitro oxidative stress (Fe2++H2O2). In animals subjected to four-vessel global ischemia for 15 min and 2–24 h reperfusion the EGb pretreatment slightly decreased LPO in forebrain homogenate. However, as detected in EGb treated group, the LPO-induced lysine conjugates are attenuated in comparison to non-treated IRI animals. EGb significantly improved parameters which indicate forebrain protein oxidative damage after IRI. The intensity of tryptophane fluorescence was increased by the 18.2% comparing to non-treated IRI group and bityrosine fluorescence was significantly decreased in ischemic (21%) and 24 h reperfused (15.9%) group in comparison non-treated IRI group. In addition, the level of total free SH- groups in pre-treated animals was significantly higher comparing to non-treated animals. Our results indicate that extract of EGb 761 has potent antioxidant activity and could play a role to attenuate the IRI-induced oxidative protein modification and lipoperoxidation in the neuroprotective process.

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REFERENCES

  • Burda, J., Hrehorovská, M., Bonilla, L. G., Danielisová, V., Čížková, D., Burda, R., Némethová, M., Fando, J. L., and Salinas, M. (2003). Role of protein synthesis in the ischemic tolerance acquisition induced by transient forebrain ischemia in the rat. Neurochem. Res. 28 :1213–1219.

    Article  PubMed  CAS  Google Scholar 

  • Candelario-Jalil, E., Mhadu, N. H., Al-Dalain, S. M., Martinez, G., and Leon, O. S. (2001). Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils. Neurosci. Res. 41 :233–241.

    Article  PubMed  CAS  Google Scholar 

  • Chen, L. X., Chen, W. Z., Huang, H. L., Chen, L. X., and Xie, Z. Z. (1998). Protective effects of Ginkgo biloba extract against lysophosphatidylcholine-induced vascular endothelial cell damage. Acta. Pharmacol. Sin. 19 :359–363.

    CAS  Google Scholar 

  • Danielisova, V., Nemethova, M., Gottlieb, M., and Burda, J. (2005). Changes of endogenous antioxidant enzymes during ischemic tolerance acquisition. Neurochem. Res. 30 :559–565.

    Article  PubMed  CAS  Google Scholar 

  • Das, D. K., and Maulik, N. (1994). Antioxidant effectiveness in ischemia-reperfusion tissue injury. Methods Enzymol. 233 :601–610.

    PubMed  CAS  Google Scholar 

  • Davies, K. J., Delsignore, M. E., and Lin, S. W. (1987). Protein damage and degradation by oxygen radicals. II. Modification of amino acids. J. Biol. Chem. 262 :9902–9907.

    PubMed  CAS  Google Scholar 

  • Davies, M. J., Fu, S., Wang, H., and Dean, R. T. (1999). Stable markers of oxidant damage to proteins and their application in the study of human disease. Free Radic. Biol. Med. 27 :1151–1163.

    Article  PubMed  CAS  Google Scholar 

  • Dirnagl, U., Lindauer, U., Them, A., Schreiber, S., Pfister, H. W., Koedel, U., Reszka, R., Freyer, D., and Villringer, A. (1995). Global cerebral ischemia in the rat: online monitoring of oxygen free radical production using chemiluminescence in vivo. J. Cereb. Blood Flow Metab. 15 :929–940.

    PubMed  CAS  Google Scholar 

  • Donato, G., Volpentesta, G., Lavano, A., Ferraro, G., Signorelli, F., Amorosi, A., Maltese, L., De Sarro, G. B., and Signorelli, C. D. (2003). Effects of Ginko Biloba and caspase inhibitors on brain ischemia in the Mongolian gerbil. J. Neurosurg. Sci. 47 :149–155.

    PubMed  CAS  Google Scholar 

  • Dousset, N., Ferretti, G., Taus, M., Valdiguie, P., and Curatola, G. (1994). Fluorescence analysis of lipoprotein peroxidation. Methods Enzymol. 233 :459–469.

    PubMed  CAS  Google Scholar 

  • Drieu, K. (1986). Preparation and definition of Ginkgo biloba extract. Presse. Med. 15 :455–1457.

    Google Scholar 

  • Dumont, E., Petit, E., Tarrade, T., and Nouvelot, A. (1992). UV-C irradiation-induced peroxidative degradation of microsomal fatty acids and proteins: Protection by an extract of Ginkgo biloba (EGb 761). Free Radical Biol. Med. 13 :197–203.

    Article  CAS  Google Scholar 

  • Freeman, B. A., and Crapo, J. D. (1982). Biology of disease: free radicals and tissue injury. Lab. Invest. 47 :412–426.

    PubMed  CAS  Google Scholar 

  • Giulivi, C., and Davies, K. J. (1994). Dityrosine: a marker for oxidatively modified proteins and selective proteolysis. Methods Enzymol. 233 :363–371.

    PubMed  CAS  Google Scholar 

  • Halliwell, B. (1989). Superoxide, iron, vascular endothelium and reperfusion injury. Free Radic. Res. Commun. 5 :325–318.

    Google Scholar 

  • Hayashi, T., Saito, A., Okuno, S., Ferrand-Drake, M., Dodd, R. L., Nishi, T., Maier, C. M., Kinouchi, H., and Chan, P. H. (2003). Oxidative damage to the endoplasmic reticulum is implicated in ischemic neuronal cell death. J. Cerebr. Blood Flow Metab. 23 :1117–1128.

    CAS  Google Scholar 

  • Hrehorovska, M., Burda, J., Domorakova, I., and Mechirova, E. (2004). Effect of Tanakan on postischemic activity of protein synthesis machinery in the rat brain. Gen. Physiol. Biophys. 23 :457–465.

    PubMed  CAS  Google Scholar 

  • Hu, M. L. (1994). Measurement of protein thiol groups and glutathione in plasma. Methods Enzymol. 233 :380–385.

    PubMed  CAS  Google Scholar 

  • Ikeda, Y., and Long, D. M. (1990). The molecular basis of brain injury and brain edema: the, role of oxygen free radicals. Neurosurgery 27 :1–11.

    Article  PubMed  CAS  Google Scholar 

  • Janssens, D., Remacle, J., Drieu, K., and Michiels, C. (1999). Protection of mitochondrial respiration activity by bilobalide. Biochem. Pharmacol. 58 :109–119.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan, P., Doval, M., Majerova, Z., Lehotsky, J., and Racay, P. (2000). Iron-induced lipid peroxidation and protein modification in endoplasmic reticulum membranes. Protection by stobadine. Int. J. Biochem. Cell. Biol. 32 :539–547.

    Article  PubMed  CAS  Google Scholar 

  • Kirino, T. (1982). Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 239:57–69.

    Article  PubMed  CAS  Google Scholar 

  • Krieglstein, J., Beck, T., and Seibert, A. (1996). Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism. Life Sci. 39 :2327–2334.

    Article  Google Scholar 

  • Lehotsky, J., Kaplan, P., Racay, P., Matejovicova, M., Drgova, A., and Mezesova, V. (1999). Membrane ion transport systems during oxidative stress in rodent brain: protective effect of stobadine and other antioxidants. Life Sci. 65 :1951–1958.

    Article  PubMed  CAS  Google Scholar 

  • Lehotský, J., Kaplán, P., Matejovičová, M., Murín, R., Račay, P., and Raeymaekers, L. (2002). Ion transport systems as targets of free radicals during ischemia/reperfusion injury. Gen. Physiol. Biophys. 21 :1–37.

    Google Scholar 

  • Lehotský, J., Kaplán, P., Babušíková, E., Strapková, A., and Murín, R. (2003). Molecular pathways of endoplasmic reticulum dysfunctions: Possible cause of cell death in the nervous system. Physiol. Res. 52 :69–273.

    Google Scholar 

  • Lehotský, J., Murín, R., Strapková, A., Uríková, A., Tatarková, Z., and Kaplán, P. (2004). Time course of ischemia/reperfusion-induced oxidative modification of neural proteins in rat forebrain. Gen. Physiol. Biophys. 23 :401–415.

    PubMed  Google Scholar 

  • Lin, J. Y., Cheng, F. C., Chung, S. Y., and Lin, M. C. (2004). Ginkgo biloba extract (EGb761) and FK506 preserve energy metabolites in the striatum during focal cerebral ischemia and reperfusion in gerbils monitored by microdialysis. J. Biomed Sci. 11 :611–616.

    PubMed  Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193 :265–275.

    PubMed  CAS  Google Scholar 

  • Matejovicova, M., Machac, S., Lehotsky, J., Jakus, J., and Mezesova, V. (1996). Synaptosomal Na, K-ATPase during forebrain ischemia in Mongolian gerbils. Mol. Chem. Neuropathol. 29:67–78.

    Article  PubMed  CAS  Google Scholar 

  • Marcocci, L., Packer, L., Droy-Lefaix, M. T., Sekaki, A., and Gardes-Albert, M. (1994). Antioxidant action of Ginkgo biloba extract EGb 761. Methods Enzymol. 234 :462–475.

    Article  PubMed  CAS  Google Scholar 

  • Murín, R., Drgová, A., Kaplán, P., Dobrota, D., and Lehotský, J. (2001). Ischemia/reperfusion - induced oxidative stress causes structural changes of brain membrane proteins and lipids. Gen. Physiol. Biophys. 20 :431–438.

    PubMed  Google Scholar 

  • 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. Neurosci. Lett. 214 :115–118.

    Article  PubMed  CAS  Google Scholar 

  • Nin, Y. H., Yang, X. Y., and Bao, W. S. (1999). Protective effects of Ginkgo biloba extract on cultured rat cardiomyocytes damaged by H2O2. Acta. Pharmacol. Sin. 20 :635–638.

    Google Scholar 

  • Nitatori, T., Sato, N., Waguri, S., Karasawa, Y., Araki, H., Shibanai, K., Kominami, E., and Uchiyama, Y. (1995). Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J. Neurosci. 15 :1001–1011.

    PubMed  CAS  Google Scholar 

  • Peng, H., Li, Y. F., and Sun, S. G. (2003). Effects of Ginkgo biloba extract on acute cerebral ischemia in rats analyzed by magnetic resonance spectroscopy. Acta. Pharmacol. Sin. 24 :467–471.

    PubMed  CAS  Google Scholar 

  • Phillis, J. W., and Sen, S. (1993). Oxypurinol attenuates hydroxyl radical production during ischemia/reperfusion injury of the rat cerebral cortex: an ESR study. Brain Res. 628 :309–312.

    Article  PubMed  CAS  Google Scholar 

  • Pulsinelli, W. A., Levy, D. E., and Duffy, T. E. (1983). Cerebral blood flow in the four-vessel occlusion rat model. Stroke 14 :832–83.

    PubMed  CAS  Google Scholar 

  • Siddique, M. S., Eddeb, F., Mantle, D., and Mendelow, A. D. (2000). Extracts of Ginkgo biloba and Panax ginseng protect brain proteins from free radical induced oxidative damage in vitro. Acta. Neurochir Suppl. 76 :87–90.

    PubMed  CAS  Google Scholar 

  • Solenski, N. J., Kwan, A. L., Yanamoto, H., Bennett, J. P., Kassell, N. F., and Lee, K. S. (1997). Differential hydroxylation of salicylate in core and penumbra regions during focal reversible cerebral ischemia. Stroke 28 :2545–2551.

    PubMed  CAS  Google Scholar 

  • Turan, I., and Martorano, D. (1995). Natural substances in psychiatry (Ginkgo biloba in dementia). Pharmacol. Bull. 31 :147–158.

    Google Scholar 

  • Tadano, T., Nakagawasai, O., Tanno, K., Morikawa, Y., Takahashi, N., and Kisara, K. (1998). Effect of Ginkgo biloba extract on impairment of learning induced by cerebral ischemia. Am. J. Chin. Med. 26 :127–132.

    Article  PubMed  CAS  Google Scholar 

  • Wang, H., Wang, Y., and Zhao, X. (1998). Protective effects of Folium Ginkgo extract on experimental cerebral ischemia of mice. China J. Chin. Mater. Med. 23 :169–171.

    CAS  Google Scholar 

  • Zhang, Y. Y., Li, P. F., and Li, D. (2003). Effect of Ginkgo biloba leaf extract on electroencephalography of rat with cerebral ischemia and reperfusion. Acta. Pharmacol. Sin. 24 :157–162.

    PubMed  CAS  Google Scholar 

  • Zhou, L., Ming, L., and Jiang, Q. (2000). Protective effect of extract of Folium Ginkgo on repeated cerebral ischemia-reperfusion injury. Chin. J. Integrated Tradit. West Med. 20 :356–358.

    CAS  Google Scholar 

  • Zini, I., Tomasi, A., Grimaldi, R., Vannini, V., and Agnati, L. F. (1992). Detection of free radicals during brain ischemia and reperfusion by spin trapping and microdialysis. Neurosci. Lett. 138 :279–282.

    Article  PubMed  CAS  Google Scholar 

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ACKNOWLEDGEMENTS

Presented as Abstract on the 5th International Symposium on Experimental and Clinical Neurobiology, Tatranska Lomnica-Stara Lesna, Slovak Republic, September 2005. This study was supported by a research grants: VEGA No. 034/03 and 3380/06 and APVT No. 51-013802.

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  1. Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University, MalaHora 4, SK-03601, Martin, Slovakia

    A. Uríková, E. Babušíková, D. Dobrota, A. Drgová, P. Kaplán, Z. Tatarková & J. Lehotský

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  1. A. Uríková
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  2. E. Babušíková
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  3. D. Dobrota
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  7. J. Lehotský
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Uríková, A., Babušíková, E., Dobrota, D. et al. Impact of Ginkgo Biloba Extract EGb 761 on Ischemia/Reperfusion – Induced Oxidative Stress Products Formation in Rat Forebrain. Cell Mol Neurobiol 26, 1341–1351 (2006). https://doi.org/10.1007/s10571-006-9030-3

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