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Melatonin prevents oxidative stress and inhibits reactive gliosis induced by hyperhomocysteinemia in rats

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Abstract

Homocysteine (Hcy), an independent risk factor for atherosclerosis, undergoes auto-oxidation and generates reactive oxygen species, which are thought to be main cause of Hcy neurotoxicity. However, the mechanisms leading to neurodegenerative disorders are poorly understood because studies that have investigated the potential neurotoxicity of hyperhomocysteinemia in vivo are scarce. The purpose of this study was to test whether daily administration of methionine, which induces hyperhomocysteinemia, causes glial hyperactivity, and also to investigate the protective effects of melatonin on the brain tissue against oxidative stress of Hcy in rats. There was a significant development of oxidative stress as indicated by an increase in malondialdehyde + 4-hydroxyalkenals in hippocampus and cortex of hyperhomocysteine mic rats, whereas significant reduction was found in the activity of glutathione peroxidase (GSH-Px). Co-treatment with melatonin inhibited the elevation of lipid peroxidation and significantly increased GSH-Px activity in the brain regions studied. Western blot analysis revealed an increase in glial fibrillary acidic protein (GFAP) contents both in hippocampus and frontal cortex (p < 0.001) of hyperhomocysteinemic rats compared to the controls. Administration of melatonin significantly decreased GFAP contents in hippocampus and cortex (p < 0.05). S100B contents increased only in frontal cortex in hyperhomocysteinemic rats compared to the control (p < 0.01) and was inhibited by melatonin treatment (p < 0.01). The present findings show that Hcy can sensitize glial cells, a mechanism which might contribute to the pathogenesis of neurodegenerative disorders, and further suggest that melatonin can be involved in protecting against the toxicity of Hcy by inhibiting free radical generation and stabilizing glial cell activity.

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Abbreviations

GFAP:

glial fibrillary acidic protein

GSH-Px:

glutathione peroxidase

Hcy:

homocysteine

LOP:

lipid peroxidation

Mel:

melatonin

References

  1. Finkelstein, J. D. (2000) Semin. Thromb. Hemost., 26, 219–225.

    Article  CAS  PubMed  Google Scholar 

  2. Ho, P. I., Ortiz, D., Rogers, E., and Shea, T. B. (2002) J. Neurosci. Res., 70, 694–702.

    Article  CAS  PubMed  Google Scholar 

  3. Hankey, G. J., and Eikelboom, J. W. (1999) Lancet, 354, 407–413.

    CAS  PubMed  Google Scholar 

  4. Lipton, S. A., Kim, W. K., Choi, Y. B., Kumar, S., D’Emilia, D. M., Rayudu, P. V., Arnelle, D. R., and Stamler, J. S. (1997) Proc. Natl. Acad. Sci. USA, 94, 5923–5928.

    Article  CAS  PubMed  Google Scholar 

  5. Stamler, J. S., Osborne, J. A., Jaraki, O., Rabbani, L. E., Mullins, M., Singel, D., and Loscalzo, J. (1993) J. Clin. Invest., 91, 308–318.

    CAS  PubMed  Google Scholar 

  6. Heinecke, J. W. (1988) in Oxyradicals in Molecular Biology and Pathology (Cerruti, P. A., Fridovich, I., and McCord, J. M., eds.) Alan R. Liss, New York, pp. 443–457.

    Google Scholar 

  7. Upchurch, G. R., Jr., Welch, G. N., Fabian, A. J., Freedman, J. E., Johnson, J. L., Keaney, J. F., Jr., and Loscalzo, J. (1997) J. Biol. Chem., 272, 17012–17017.

    CAS  PubMed  Google Scholar 

  8. Maler, J. M., Seifert, W., Huther, G., Wiltfang, J., Ruther, E., Kornhuber, J., and Bleich, S. (2003) Neurosci. Lett., 347, 85–88.

    Article  CAS  PubMed  Google Scholar 

  9. Moonen, G., Rogister, B., Leprince, P., Rigo, J. M., Delree, P., Lefebvre, P. P., and Schoenen, J. (1990) Progr. Brain Res., 86, 63–73.

    CAS  Google Scholar 

  10. Reier, P. J., and Houle, J. D. (1988) Adv. Neurol., 47, 87–138.

    CAS  PubMed  Google Scholar 

  11. O’Callaghan, J. P., Jensen, K. F., and Miller, D. B. (1995) Neurochem. Int., 26, 115–124.

    CAS  PubMed  Google Scholar 

  12. Baydas, G., Nedzvetskii, V. S., Tuzcu, M., Yasar, A., and Kirichenko, S. V. (2003) Eur. J. Pharmacol., 462, 67–71.

    Article  CAS  PubMed  Google Scholar 

  13. Liedtke, W., Edekmann, W., Bieri, P. L., Chiu, F. C., Cowan, N. J., Kucherlapati, R., and Raine, C. S. (1996) Neuron, 17, 607–615.

    Article  CAS  PubMed  Google Scholar 

  14. Cerutti, S. M., and Chadi, G. (2000) Cell. Biol. Int., 24, 35–49.

    Article  CAS  PubMed  Google Scholar 

  15. Kligman, D., and Marshak, D. R. (1985) Proc. Natl. Acad. Sci. USA, 82, 7136–7139.

    CAS  PubMed  Google Scholar 

  16. Persson, L., Hardemark, H. G., Gustafsson, J., Rundstrom, G., Mendel-Hartvig, I., Esscher, T., and Pahlman, S. (1987) Stroke, 18, 911–918.

    CAS  PubMed  Google Scholar 

  17. Baydas, G., Reiter, R. J., Yasar, A., Tuzcu, M., Akdemir, I., and Nedzvetskii, V. S. (2003) Free Rad. Biol. Med., 35, 797–804.

    Article  CAS  PubMed  Google Scholar 

  18. Baydas, G., Tuzcu, M., Yasar, A., and Baydas, B. (2004) Acta Diabetol., 41, 123–128.

    Article  CAS  PubMed  Google Scholar 

  19. Tan, D. X., Chen, L. D., Poeggeler, B., Manchester, L. C., and Reiter, R. J. (1993) Endocrine J., 1, 57–60.

    Google Scholar 

  20. Zhang, H., Squadrito, G. L., and Pryor, W. A. (1998) Biochem. Biophys. Res. Commun., 251, 83–87.

    CAS  PubMed  Google Scholar 

  21. Bagi, Z., Cseko, C., Toth, E., and Koller, A. (2003) Am. J. Physiol. Heart. Circ. Physiol., 285, 2277–2283.

    Google Scholar 

  22. Lawrence, R. A., and Burk, R. F. (1976) Biochem. Biophys. Res. Commun., 71, 952–958.

    Article  CAS  PubMed  Google Scholar 

  23. Baydas, G., Gursu, M. F., Cikim, G., and Canatan, H. (2002) J. Pineal Res., 32, 63–64.

    Article  CAS  PubMed  Google Scholar 

  24. Baydas, G., Yilmaz, O., Celik, S., Yasar, A., and Gursu, M. F. (2002) Arch. Med. Res., 33, 515–519.

    CAS  PubMed  Google Scholar 

  25. Kim, J. P., Koh, J. Y., and Choi, D. W. (1987) Brain Res., 437, 103–110.

    Article  CAS  PubMed  Google Scholar 

  26. Reutens, S., and Sachdev, P. (2002) Int. J. Geriatr. Psychiatry, 17, 859–864.

    Article  PubMed  Google Scholar 

  27. Jara-Prado, A., Ortega-Vazquez, A., Martinez-Ruano, L., Rios, C., and Santamaria, A. (2003) Neurotox. Res., 5, 237–243.

    PubMed  Google Scholar 

  28. Dayal, S., Arning, E., Bottiglieri, T., Boger, R. H., Sigmund, C. D., Faraci, F. M., and Lentz, S. R. (2004) Stroke, 35, 1957–1962.

    Article  CAS  PubMed  Google Scholar 

  29. Goth, L., and Vitai, M. (2003) Free Rad. Biol. Med., 35, 882–888.

    CAS  PubMed  Google Scholar 

  30. Osuna, C., Reiter, R. J., Garcia, J. J., Karbownik, M., Tan, D. X., Calvo, J. R., and Manchester, L. C. (2002) Pharmacol. Toxicol., 90, 32–37.

    Article  CAS  PubMed  Google Scholar 

  31. Baydas, G., Kutlu, S., Naziroglu, M., Canpolat, S., Sandal, S., Ozcan, M., and Kelestimur, H. (2003) J. Pineal Res., 34, 36–39.

    Article  CAS  PubMed  Google Scholar 

  32. Yamamato, M., Hara, H., and Adachi, T. (2000) FEBS Lett., 486, 159–162.

    Google Scholar 

  33. Bates, K. A., Fonte, J., Robertson, T. A., Martins, R. N., and Harvey, A. R. (2002) Neuroscience, 113, 785–796.

    Article  CAS  PubMed  Google Scholar 

  34. Banati, R. B., Gehrmann, J., Schubert, P., and Kreutzberg, G. W. (1993) Glia, 7, 111–118.

    CAS  PubMed  Google Scholar 

  35. Baydas, G., Reiter, R. J., Nedzvetskii, V. S., Yasar, A., Tuzcu, M., Ozveren, F., and Canatan, H. (2003) Toxicol. Lett., 137, 169–174.

    Article  CAS  PubMed  Google Scholar 

  36. Baydas, G., Reiter, R. J., Nedzvetskii, V. S., Nerush, P. A., and Kirichenko, S. V. (2002) J. Pineal Res., 33, 134–139.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Firat University, Elazig, 23119, Turkey

    G. Baydas, M. Ozer, A. Yasar & S. T. Koz

  2. Department of Biology, Faculty of Science, Firat University, Elazig, Turkey

    M. Tuzcu

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  1. G. Baydas
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  2. M. Ozer
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  3. A. Yasar
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  4. S. T. Koz
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  5. M. Tuzcu
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Correspondence to G. Baydas.

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Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM05-001, June 12, 2005.

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Baydas, G., Ozer, M., Yasar, A. et al. Melatonin prevents oxidative stress and inhibits reactive gliosis induced by hyperhomocysteinemia in rats. Biochemistry (Moscow) 71 (Suppl 1), S91–S95 (2006). https://doi.org/10.1134/S0006297906130153

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  • DOI: https://doi.org/10.1134/S0006297906130153

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