Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage

Russel J Reiter, Dun Xian Tan, Eloisa Gitto, Rosa M. Sainz, Juan C. Mayo, Josefa Leon, Lucien C. Manchester, A. Vijayalaxmi, Ertugrul Kilic, Ülkan Kilic

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

This review briefly summarizes the actions of melatonin in reducing molecular damage caused by free radicals and associated oxygen- and nitrogen-based reactants. All the mechanisms by which melatonin is protective of such a wide variety of molecules, i.e. lipids, proteins, DNA, etc., and in such widely diverse areas of the cell and different organs are likely not yet all identified. Melatonin actions that have been identified include its ability to directly neutralize a number of toxic reactants and stimulate antioxidative enzymes. Furthermore, several metabolites that are formed when melatonin neutralizes damaging reactants are themselves scavengers suggesting that there is a cascade of reactions that greatly increase the efficacy of melatonin in stymying oxidative mutilation. Suggested, but less well defined, processes which may contribute to melatonin's ability to reduce oxidative stress include stimulation of glutathione synthesis (an important antioxidant which is at high concentrations within cells), reducing electron leakage from the mitochondrial electron transport chain (which would reduce free radical generation), limiting cytokine production and inflammatory processes (actions that would also lower toxic reactant generation), and synergistic effects with other classical antioxidants (e.g. vitamins C, E and glutathione). Clearly which of these multiple mechanisms contribute to melatonin's high efficacy in curtailing oxidative damage remains to be clarified. Likewise, it is possible that the key action of melatonin in reducing molecular damage induced by oxygen and nitrogen-based metabolites remains to be identified. Finally, the review summarizes some of the large amount of data documenting the ability of melatonin to limit molecular and organ damage in two situations, i.e. ischemia-reperfusion and ionizing radiation, where free radicals are generally conceded as being responsible for much of the resulting tissue destruction.

Original languageEnglish (US)
Pages (from-to)159-170
Number of pages12
JournalPolish Journal of Pharmacology
Volume56
Issue number2
StatePublished - 2004

Fingerprint

Melatonin
Pharmacology
Free Radicals
Poisons
Glutathione
Nitrogen
Antioxidants
Oxygen
Cohort Effect
Electron Transport
Ionizing Radiation
Vitamin E
Ascorbic Acid
Reperfusion
Oxidative Stress
Ischemia
Electrons
Cytokines
Lipids
DNA

Keywords

  • Antioxidant
  • Free Radicals
  • Ionizing radiation
  • Ischemia-reperfusion injury
  • Melatonin
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmacology

Cite this

Reiter, R. J., Tan, D. X., Gitto, E., Sainz, R. M., Mayo, J. C., Leon, J., ... Kilic, Ü. (2004). Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage. Polish Journal of Pharmacology, 56(2), 159-170.

Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage. / Reiter, Russel J; Tan, Dun Xian; Gitto, Eloisa; Sainz, Rosa M.; Mayo, Juan C.; Leon, Josefa; Manchester, Lucien C.; Vijayalaxmi, A.; Kilic, Ertugrul; Kilic, Ülkan.

In: Polish Journal of Pharmacology, Vol. 56, No. 2, 2004, p. 159-170.

Research output: Contribution to journalArticle

Reiter, RJ, Tan, DX, Gitto, E, Sainz, RM, Mayo, JC, Leon, J, Manchester, LC, Vijayalaxmi, A, Kilic, E & Kilic, Ü 2004, 'Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage', Polish Journal of Pharmacology, vol. 56, no. 2, pp. 159-170.
Reiter, Russel J ; Tan, Dun Xian ; Gitto, Eloisa ; Sainz, Rosa M. ; Mayo, Juan C. ; Leon, Josefa ; Manchester, Lucien C. ; Vijayalaxmi, A. ; Kilic, Ertugrul ; Kilic, Ülkan. / Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage. In: Polish Journal of Pharmacology. 2004 ; Vol. 56, No. 2. pp. 159-170.
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