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Melatonin and Tryptophan Derivatives as Free Radical Scavengers and Antioxidants

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Tryptophan, Serotonin, and Melatonin

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 467))

Abstract

Several tryptophan derivatives function as free radical scavengers and antioxidants. The molecule that has been most widely investigated in this regard is N-acetyl-5-methoxytryptamine (melatonin); however, pinoline (6-methoxy-1,2,3,4-tetrahydro-β-carboline) and N-acetylserotonin also possess free radical scavenging activity. Experimental studies have shown that melatonin directly scavenges the hydroxy radical, peroxyl radical, peroxynitrite anion, and singlet oxygen. Furthermore, this tryptophan derivative stimulates a number of antioxidative enzymes and stabilizes cell membranes; this latter action helps membranes to resist free radical damage. While the antioxidative actions of most molecules are limited by their specific intracellular distribution, e.g., vitamin E in lipid-rich membranes, melatonin’s antioxidative actions include the protection of lipids in the cell membrane, proteins in the cytosol, and DNA in the nucleus. Furthermore, melatonin crosses all morphophysiological barriers and enters equally well all cells in the organism.

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References

  • Barchas, J., DaCosta, F., and Spector, S., 1967, Acute pharmacology of melatonin, Nature 214:919–920.

    Article  PubMed  CAS  Google Scholar 

  • Beal, M.F., 1995, Aging, energy, and oxidative stress in neurodegenerative diseases, Ann. Neurol. 38:357–366.

    Article  PubMed  CAS  Google Scholar 

  • Beckman, K.B. and Ames, B.N, 1997, Oxidative decay of Dann, J. Biol. Chem. 272:19633–19636.

    Article  PubMed  CAS  Google Scholar 

  • Chen, T.Y. and Tang, P.L., 1996, Characterization of the antioxidant effects of melatonin and related indoleamines in vitro, J. Pineal Res. 20:187–191.

    Article  Google Scholar 

  • Costa, E.J.X., Lopes, R.H., and Lamy-Freund, M.T., 1995, Permeability of pure lipid bilayers to melatonin, J. Pineal Res. 19:123–126.

    Article  PubMed  CAS  Google Scholar 

  • Crow, J.P., Beckman, J.S., and McCord, J.M., 1995, Sensitivity of the zinc-thiolate mioety of yeast alcohol dehydrogenase to hypochorite and peroxynitrite, Biochemistry 34:3544–3552.

    Article  PubMed  CAS  Google Scholar 

  • Finnochiaro, L.M.E. and Glikin, G.C., 1998, Intracellular melatonin distribution in cultured cell lines, J. Pineal Res. 24:22–34.

    Article  Google Scholar 

  • Garcia, J.J., Reiter, R.J., Ortiz, G.G., Oh, C.S., Tang, L., Yu, B.P., and Escames, G., 1998, Melatonin enhances tamoxifen’s ability to prevent the reduction in microsomal membrane fluidity induced by lipid peroxidation, J. Membr. Biol. 162:59–65.

    Article  PubMed  CAS  Google Scholar 

  • Gilad, E., Cuzzocrea, S., Zingarelli, B, Salzman, A.L., and Szabo, C., 1997, Melatonin is a scavenger of peroxynitrite, Life Sci. 60:PL169–PL174.

    Article  PubMed  CAS  Google Scholar 

  • Halliwell, B. and Gutteridge, J.M.C., 1985, Oxygen radicals and the nervous system, Trends Neurosci. 8:22–26.

    Article  CAS  Google Scholar 

  • Halliwell, B. and Gutteridge, J.M.C., 1990, Role of free radicals and catalytic metal ions in human disease: a review, Methods Enzymol. 186:1–85.

    Article  PubMed  CAS  Google Scholar 

  • Hardeland, R., Reiter, R.J., Poeggeler, B., and Tan, D.X., 1993, The significance of the metabolism of the neurohormone melatonin: antioxidant protection and formation of bioactive substances, Neurosci. Biobehav. Res. 17:347–357.

    Article  CAS  Google Scholar 

  • Harman, D., 1992, Free radical theory of aging, Mutat. Res. 275:257–266.

    Article  PubMed  CAS  Google Scholar 

  • Huether G., 1993, The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates, Experientia 49:665–670.

    Article  PubMed  CAS  Google Scholar 

  • Ianas, O., Olinescu, R., and Badescu, I., 1991, Melatonin involvement in oxidative stress, Endocrinol. 29:147–153.

    CAS  Google Scholar 

  • Lezoualc’h, F., Sparapani, M., and Behl, C., 1998, N-acetylserotonin (normelatonin) and melatonin protect neurons against oxidative challenges and suppress the activity of the transcription factor NF-κB, J. Pineal Res. 24:168–178.

    Article  CAS  Google Scholar 

  • Longoni, B., Pryor, W.A., and Marchiafava P., 1997, Inhibition of lipid peroxidation by N-acetylserotonin and its role in retinal physiology, Biochem. Biophys. Res. Commun. 233:778–780.

    Article  PubMed  CAS  Google Scholar 

  • Matuszek, Z., Reszka, K.J., and Chignell, C.F., 1997, Reaction of melatonin and related indoles with hydroxyl radicals: ESR and spin trapping investigations, Free Radical Biol. Med. 23:367–372.

    Article  Google Scholar 

  • Menendez-Pelaez, A. and Reiter, R.J., 1993, Distribution of melatonin in mammalian tissues: relative importance of nuclear versus cytosolic localization, J. Pineal Res. 15:59–69.

    Article  PubMed  CAS  Google Scholar 

  • Menendez-Pelaez, A., Poeggeler, B., Reiter, R.J., Barlow-Waiden, L., Pablos, M.I., and Tan D.X., 1993, Nuclear localization of melatonin in different mammalian tissues, J. Cell. Biochem. 53:572–582.

    Article  Google Scholar 

  • Morrey, K.M., McLauhlan, J.A., Sherkin, C.D., and Barouche, O., 1994, Activation of human monocytes by the pineal hormone melatonin, J. Immunol. 153:2671–2680.

    PubMed  CAS  Google Scholar 

  • Nordlund, J.J. and Lerner, A.B., 1976, The effects of oral melatonin on skin color and the release of pituitary hormones, J. Clin. Endocrinol. Metab. 45:768–774.

    Article  Google Scholar 

  • Pähkla, R., Zilmer, M., Kullisar, T., and Rägo, L., 1998, Comparison of the antioxidant activity of melatonin and pinoline in vitro, J. Pineal Res. 24:96–101.

    Article  PubMed  Google Scholar 

  • Pieri, C., Marra, M., Moroni, F., Recchioni, R., and Marcheselli, F., 1994, Melatonin: a peroxyl radical scavenger more efficient than vitamin E, Life Sci. 55:PL271–PL276.

    Article  PubMed  CAS  Google Scholar 

  • Pieri, C., Moroni, F., Marra, M., Marcheselli, F., and Recchioni, R., 1995, Melatonin is an efficient antioxidant, Arch, Geront l. Geriatrics 20:159–165.

    Article  CAS  Google Scholar 

  • 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 chain-breaking antioxidants ascorbate, trolox and glutathione, Neuroendocrinol. Lett. 17:87–92.

    CAS  Google Scholar 

  • Poeggeler, B., Reiter, R.J., Hardeland, R., Tan, D.X., and Barlow-Walden, L.R., 1996, Melatonin and structurally-related endogenous indoles act as potent electron donors and radical scavengers, Redox Report 2:179–184.

    CAS  Google Scholar 

  • Pryor, W. and Squadrito, G., 1995, The chemistry of peroxynitrite: a product from the reaction of nitric oxide with Superoxide, Am. J. Physiol. 268:L699–L722.

    PubMed  CAS  Google Scholar 

  • Radi, R., Beckman, J.S., Bush, K.M., and Freeman, B.A., 1991, Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of Superoxide and nitric oxide, J. Biol Chem. 266:4244–4250.

    PubMed  CAS  Google Scholar 

  • Reiter, R.J., 1991, Pineal melatonin: cell biology of its synthesis and of its physiological interactions, Endocrine Rev. 12:151–180.

    Article  CAS  Google Scholar 

  • Reiter, R.J., 1998a, Oxidative damage in the central nervous system: protection by melatonin, Prog. Neurobiol. 56:359–367.

    Article  PubMed  CAS  Google Scholar 

  • Reiter, R.J., Pablos, M.I., Agapito, M.I., and Guerrero, J.M., 1996a, Melatonin in the context of the free radical theory of aging, Ann. N. Y. Acad. Sci. 786:362–378.

    Article  PubMed  CAS  Google Scholar 

  • Reiter, R.J., Oh, C.S., and Fujimori, O., 1996b, Melatonin: its intracellular and genomic actions, Trends Endocrinol. Metab. 7:22–27.

    Article  PubMed  CAS  Google Scholar 

  • Reiter, R.J., Tang, L., Garcia, J.J., and Muñoz-Hoyos, A., 1997, Pharmacological actions of melatonin in oxygen radical pathophysiology, Life Sci. 60:2255–2271.

    Article  PubMed  CAS  Google Scholar 

  • Reiter, R.J., Carneiro, R.C., and Oh, C.S., 1997, Melatonin in relation to cellular antioxidative defense mechanisms, Horm. Metab. Res. 29:363–372.

    Article  PubMed  CAS  Google Scholar 

  • Reiter, R.J., Garcia, J.J., and Pie, J.S., 1998b, Oxidative toxicity in models neurodegeneration, Restr. Neurol. Neurosci. 12:135–142.

    CAS  Google Scholar 

  • Shida, C.S., Castrucci, A.M.L., and Lamy-Freund, M.T., 1994, High solubility in aqueous medium, J. Pineal Res. 16:198–201.

    Article  PubMed  CAS  Google Scholar 

  • Sies, H., Sharov, V.S., Klotz, L.O., and Briviba, K., 1997, Glutathione peroxidase protects against peroxynitrite-mediated oxidations, J. Biol. Chem. 272:27812–27817.

    Article  PubMed  CAS  Google Scholar 

  • Stasica, P., Ulanski, P., and Rosiak, J.M., 1998, Melatonin as a hydroxy radical scavenger, J. Pineal Res. 25:65–66.

    Article  PubMed  CAS  Google Scholar 

  • Susa, N., Ueno, S., Furukawa, Y., Ueda, J., and Sugiyama, M., 1997, Potent protective effect of melatonin on chromium (VI) induced DNA single-strand breaks, cytotoxicity, and lipid peroxidation in primary cultures of rat hepatocytes, Toxicol. Appl. Pharmacol. 144:377–384.

    Article  PubMed  CAS  Google Scholar 

  • Tan, D.X., Chen, L.D., Poeggeler, B. Manchester, L.C., and Reiter, R.J., 1993, Melatonin: a potent, endogenous hydroxyl radical scavenger, Endocrine J. 1:57–60.

    Google Scholar 

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© 1999 Springer Science+Business Media New York

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Reiter, R.J., Tan, Dx., Cabrera, J., D’Arpa, D. (1999). Melatonin and Tryptophan Derivatives as Free Radical Scavengers and Antioxidants. In: Huether, G., Kochen, W., Simat, T.J., Steinhart, H. (eds) Tryptophan, Serotonin, and Melatonin. Advances in Experimental Medicine and Biology, vol 467. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4709-9_48

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  • DOI: https://doi.org/10.1007/978-1-4615-4709-9_48

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7133-5

  • Online ISBN: 978-1-4615-4709-9

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