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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Barchas, J., DaCosta, F., and Spector, S., 1967, Acute pharmacology of melatonin, Nature 214:919–920.
Beal, M.F., 1995, Aging, energy, and oxidative stress in neurodegenerative diseases, Ann. Neurol. 38:357–366.
Beckman, K.B. and Ames, B.N, 1997, Oxidative decay of Dann, J. Biol. Chem. 272:19633–19636.
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.
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.
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.
Finnochiaro, L.M.E. and Glikin, G.C., 1998, Intracellular melatonin distribution in cultured cell lines, J. Pineal Res. 24:22–34.
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.
Gilad, E., Cuzzocrea, S., Zingarelli, B, Salzman, A.L., and Szabo, C., 1997, Melatonin is a scavenger of peroxynitrite, Life Sci. 60:PL169–PL174.
Halliwell, B. and Gutteridge, J.M.C., 1985, Oxygen radicals and the nervous system, Trends Neurosci. 8:22–26.
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.
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.
Harman, D., 1992, Free radical theory of aging, Mutat. Res. 275:257–266.
Huether G., 1993, The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates, Experientia 49:665–670.
Ianas, O., Olinescu, R., and Badescu, I., 1991, Melatonin involvement in oxidative stress, Endocrinol. 29:147–153.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Pieri, C., Moroni, F., Marra, M., Marcheselli, F., and Recchioni, R., 1995, Melatonin is an efficient antioxidant, Arch, Geront l. Geriatrics 20:159–165.
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.
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.
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.
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.
Reiter, R.J., 1991, Pineal melatonin: cell biology of its synthesis and of its physiological interactions, Endocrine Rev. 12:151–180.
Reiter, R.J., 1998a, Oxidative damage in the central nervous system: protection by melatonin, Prog. Neurobiol. 56:359–367.
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.
Reiter, R.J., Oh, C.S., and Fujimori, O., 1996b, Melatonin: its intracellular and genomic actions, Trends Endocrinol. Metab. 7:22–27.
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.
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.
Reiter, R.J., Garcia, J.J., and Pie, J.S., 1998b, Oxidative toxicity in models neurodegeneration, Restr. Neurol. Neurosci. 12:135–142.
Shida, C.S., Castrucci, A.M.L., and Lamy-Freund, M.T., 1994, High solubility in aqueous medium, J. Pineal Res. 16:198–201.
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.
Stasica, P., Ulanski, P., and Rosiak, J.M., 1998, Melatonin as a hydroxy radical scavenger, J. Pineal Res. 25:65–66.
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.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media New York
About this chapter
Cite this chapter
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
Download citation
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
eBook Packages: Springer Book Archive