The Indoleamine Melatonin as a Free Radical Scavenger, Electron Donor, and Antioxidant

In Vitro And In Vivo Studies
  • R. J. Reiter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 398)


Following its discovery in bovine pineal tissue in the late 1950s (Lerner et al, 1958) melatonin was functionally linked to the reproductive system (Hoffman and Reiter, 1965). Soon after its discovery, the pineal gland, which is a primary source for circulating melatonin, was shown to be functionally dependent on the photoperiodic cycle (Quay, 1964; Snyder et al., 1964), found to regulate photoperiod-mediated reproductive physiology (Czyba et al., 1964; Hoffman and Reiter, 1965, Reiter, 1973), and shown to depend on its sympathetic innervation for its activity (Reiter and Hester, 1966).


Lipid Peroxidation Free Radical Scavenger Pineal Gland Free Radical Damage Efficient Scavenger 
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  1. Abe, M., Reiter, R.J., Orhii, PB., Hara, M., and Poeggeler, B., 1994, Inhibitory effect of melatonin on cataract formation in newborn rats: Evidence for an antioxidative role for melatonin. J. Pineal Res. 17: 94.CrossRefGoogle Scholar
  2. Arendt, J., Aldhous, M., English, J., Marks, V., and Arendt, J.H., 1987, Some effects of jet lag and their alleviation by melatonin. Ergonomics 30: 1379.CrossRefGoogle Scholar
  3. Armstrong, S.M., and Redman, J.R., 1993, Melatonin and circadian rhythmicity, in: Melatonin, H.S. Yu and R.J. Reiter, Eds., CRC Press, Boca Raton, pp. 187–224.Google Scholar
  4. Barlow-Walden, L.R., Reiter, R.J., Abe, M., Pablos, M.I., Menendez-Palez, A., Chen, L.D., and Poeggeler, B., 1995, Melatonin stimulates brain glutathione peroxidase activity. Neurochem Int. 26: 497.CrossRefGoogle Scholar
  5. Burke, T.H., and Sandstrom, P.A., 1994, Oxidative stress as a mediator of apoptosis. Immunol. Today, 15: 7.CrossRefGoogle Scholar
  6. Cagnoli, C., Atabay, C., Kharlamova, E., and Manev, H., 1995, Melatonin protects nuerons from singlet oxygen-induced opoptosis. J. Pineal Res., in press.Google Scholar
  7. Chen, L.D., Kumar, P., Reiter, R.J., Tan, D.X., Manchester, L.C., Chambers, J.P., Poeggeler, B., and Saarela, S., 1994, Melatonin prevents the suppression of cardiac Ca2+ — stimulated ATPase activity. Amer. J. Physiol. 267: E57.Google Scholar
  8. Czyba, J.C., Girod, C., and Durant, M., 1964, Sur 1’ antagonism épiphyseo-hypophysaire et les variations saisonnières de la spermatogénèse chez le Hamster doré (Mesocricetus auratus). C.R. Soc. Biol. 158: 742.Google Scholar
  9. Daniels, W.M.V., Reiter, R.J., Melchiorri, D., Sewerynek, E., Pablos, M.I. and Ortiz, G.G., 1995, Melatonin counteracts lipid peroxidation induced by carbon tetrachloride but does not restore glucose-6-phosphatase activity. J. Pineal Res., in pressGoogle Scholar
  10. Floyd, R.A., 1993, Basic free radical biochemistry, in: Free Radicals in Aging, B.P. Yu, Ed., CRC Press, Boca Raton, pp. 39–56.Google Scholar
  11. Giusti, P., Gusella, M., Lipartiti, D., Milam, D. Zhu, W., Vicini, S., and Manev, H., 1995, Melatonin protects primary cultures of cerebellar granule neurons from kainate but not from N-methyl aspartate toxicity. Exp. Neurol. 131: 39.CrossRefGoogle Scholar
  12. Goldman, B.D., and Nelson, R.J., 1993, Melatonin and seasonality in mammals, in: Melatonin, H.S. Yu and R.J. Reiter, Eds., CRC Press, Boca Raton, pp. 225–252.Google Scholar
  13. Hoffman, R.A. and Reiter, R.J., 1965, Pineal gland: Influence on gonads of male hamsters. Science 148: 1609.CrossRefGoogle Scholar
  14. Koppenal, W.H., 1994, Chemistry of iron and copper in radical reactions, in: Free Radical Damage and Its Control, C.A. Rice-Evans and R.H. Burdon, Eds., Elsevier, Amsterdam, pp. 3–24.CrossRefGoogle Scholar
  15. Lerner, A.B., Case, J.D., Takahashi, Y., Lee, Y., and Mori, W., 1958, Isolation of melatonin, a pineal gland factor that lightens melanocytes. J. Amer. Chem. Soc. 8: 2587.CrossRefGoogle Scholar
  16. Malpaux, B., Chemineau, P., and Pelletier, J., 1993, Melatonin and reproduction in sheep and goats, in: Melatonin, H.S. Yu and R.J. Reiter, Eds., CRC Press, Boca Raton, pp. 253–288.Google Scholar
  17. Melchiorri, D., Reiter, R.J., Attia, A.M., Hara, M., Burgos, A., and Nistico, G., 1995a, Potent protective effect of melatonin on in vivo paraquat-induced oxidative damage in rats. Life Sci. 96: 83.CrossRefGoogle Scholar
  18. Melchiorri, D., Reiter, R.J., Sewerynek, E., Chen, L.D., and Nistico, G., 1995b, Melatonin reduces kainate-induced lipid peroxidation in homogenates of different brain regions. FASEB J., in press.Google Scholar
  19. Meneghini, R., and Martin, E.L., 1993, Hydrogen peroxide and DNA damage, in: DNA and Free Radicals, B. Halliwell and O.I. Aruoma, Eds., Ellis Harwood, London, pp. 83–94.Google Scholar
  20. Pieri, C., Maria, M., Moroni, F., Decchioni, R., and Marcheselli, 1994, Melatonin: Aperoxyl radical scavenger more potent than vitamin E. Life Sci. 55: 271.CrossRefGoogle Scholar
  21. Pierrefiche, G., and Laborit, H., 1995, Oxygen free radicals, melatonin, and aging. Exp. Gerontol. 30: 213.CrossRefGoogle Scholar
  22. Pierrefiche, G., Topall, G., Courboin, G., Henriet, I., and Laborit, H., 1993, Antioxidant activity of melatonin in mice. Res. Commun. Chem. Pathol. Pharmacol. 80: 211.Google Scholar
  23. Poeggeler, B., Saarela, S., Reiter, R.J., Tan, D.X., Chen, L.D., Manchester, L.C., and Barlow-Walden, L.R., 1994 Melatonin-a highly potent endogenous radical scavenger and electron donor: New aspects of the oxidation chemistry of this indole assessed in vitro. Ann. N. Y. Acad. Sci. 738: 419.CrossRefGoogle Scholar
  24. Poeggeler, B., Reiter, R.J., Hardeland, R., Sewerynek, E., Melchiorri, D., and Barlow-Walden, L.R., 1995, Melatonin, a mediator of electron transfer and repair reactions, acts synergistically with the chainbreaking antioxidants ascorbate, trolox and glutathione. Neuorendocrinol. Lett., in press.Google Scholar
  25. Pryor, W.A., 1994, Free radicals and lipid peroxidation, in: Natural Antioxidants in Human Health and Disease, B. Frei, Eds., Academic Press, San Diego, pp. 1–24.Google Scholar
  26. Quay, W.B., 1964, Circadian and estrous rhythms in pineal melatonin and 5-hydroxyindole-3-acetic acid. Proc. Soc. Exp. Biol. Med. 114: 718.Google Scholar
  27. Reiter, R.J., 1973, Comparative physiology: Pineal gland. Annu. Rev. Physiol. 35: 305.CrossRefGoogle Scholar
  28. Reiter, R.J., 1991, Melatonin: That ubiquitously acting pineal hormone. News Physiol. Sci. 6: 223.Google Scholar
  29. Reiter, R.J., 1995, Oxidative processes and antioxidative defence mechanisms in the aging brain. FASEB J. 9: 526.Google Scholar
  30. Reiter, R.J., and Hester, R.J., 1966, Interrelationships of the pineal gland, the superior cervical ganglia and the photoperiod in the regulation of the endocrine system of hamsters. Endocrinology 79: 1168.CrossRefGoogle Scholar
  31. Reiter, R.J., and Richardson, B.A., 1980, The physiology of melatonin, in: Biochemical and Medical Aspects of Tryptophan Metabolism. O. Hayaishi, Y. Ishimura, and R. Kido, eds., Elsevier/North Holland, Amsterdam, pp. 247–256.Google Scholar
  32. Reiter, R.J., Blask, D.E., Johnson, L.Y., Rudeen, P.K., Vaughan, W.K., and Waring, P.J., 1976. Melatonin inhibition of reproduction in the male hamster: Its dependency on time of day of administration and on an intact and sympathetically innervated pineal gland. Neuroendocrinology 22: 107.CrossRefGoogle Scholar
  33. Reiter, R.J., Tan, D.X., Poeggeler, B., Menendez-Pelaez, A., Chen, L.D., and Saarela, S.. 1994. Melatonin as a free radical scavenger: Implications for aging and age-related diseases. Ann. N. Y. Acad. Sci. 719: 1.CrossRefGoogle Scholar
  34. Reiter, R.J., Melchiorri, D., Sewerynek, E., Poeggeler, B., Barlow-Walden, L.R., Chuang, J.I., Ortiz, G.G., and Acuña-Castroviejo, D., 1995, A review of the evidence supporting melatonin’s role as an antioxidant. J. Pineal Res18: 1.CrossRefGoogle Scholar
  35. Sewerynek, E., Melchiorri, D., Ortiz, G.G., Poeggeler, B., and Reiter, R.J., 1995a, Melatonin reduces H2O2-induced lipid peroxidation in homogenates of different rat brain regions. J. Pineal Res. ., in press.Google Scholar
  36. Sewerynek, E., Melchiorri, D., Chen, L.D., and Reiter, R.J., 1995b, Melatonin reduces both basal and bacterial lipopolysacchoride-induced lipid peroxidation in vivo. Free Rad. Biol. Med., in pressGoogle Scholar
  37. Sewerynek, E., Melchiorri, D., Reiter, R.J., Ortiz, G.G., and Lewinski, A., 1995, Lipopolysacchoride-induced hepatotoxicity is inhibited by the antioxidant melatonin. Eur. J. Pharmacol., in press.Google Scholar
  38. Snyder, S.H., Zweig, M., and Axelrod, J., 1964, Control of the circadian rhythm in serotonin content of the rat pineal gland. Life Sci. 3: 1175.CrossRefGoogle Scholar
  39. Tamarkin, L., Westrom, W.K., Hamill, A.I., and Goldman, B.D. 1976, Effect of melatonin on the reproductive systems of male and female Syrian hamsters. Diurnal rhythm in sensitivity to melatonin. Endocrinology 101: 631.CrossRefGoogle Scholar
  40. Tan, D.X., Chen, L.D., Poeggeler, B., Manchester, L.C., and Reiter, R.J., 1993a, Melatonin: A potent, endogenous hydroxyl scavenger. Endocrine J. 1: 57.Google Scholar
  41. Tan, D.X., Poeggeler, B., Reiter, R.J., Chen, L.D., Chen, S., Manchester, L.C., and Barlow-Walden, L. R., 1993b, The pineal hormone melatonin inhibits DNA adduct formation induced by the chemical carcinogen safrole in vivo. Cancer Lett., 70: 65.CrossRefGoogle Scholar
  42. Tan, D.S., Reiter, R.J., Chen, L.D., Poeggeler, B., Manchester, L.C., Barlow-Walden, LR., 1994, Both physiological and pharmacological levels of melatonin reduce DNA adduct formation induced by the carcinogen safrole. Carcinogenesis 15: 615.CrossRefGoogle Scholar
  43. Vijayalaxmi, Reiter, R.J., and Meltz, M.L., 1995, Melatonin protects human blood lymphocytes from radiation induced chromosome damage. Mutat. Res. 346: 23.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • R. J. Reiter
    • 1
  1. 1.Department of Cellular and Structural BiologyThe University of Texas Health Science CenterSan AntonioUSA

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