Reactive oxygen and nitrogen species and cellular and organismal decline: Amelioration with melatonin

Russel J. Reiter, Dun Xian Tan, Susanne Burkhardt

Research output: Contribution to journalReview articlepeer-review

186 Scopus citations


Cellular and organismal decline is, in part, believed to be a consequence of oxygen and nitrogen-based reactants which persistently damage macromolecules throughout a lifetime. The resulting accumulation of damaged molecules eventually seriously compromises essential functions of cells leading to their death. Excessive cellular loss causes deterioration of organ function and inevitably to the demise of the organism. The sequence of events, known as the free radical theory of aging, is widely espoused by biological gerontologists. Antioxidants are commonly employed to combat molecular damage mediated by oxygen and nitrogen-based reactants. One of these protective agents is melatonin. Melatonin has several distinct advantages as a preserver of organelle structure and function. It is widely distributed in organisms and within cells. It works via a number of mechanisms to reduce oxidative damage. Thus, melatonin scavenges a number of reactants including the hydroxyl radical (·OH), hydrogen peroxide (H2O2), nitric acid (NO·), peroxynitrite (ONOO-) and peroxynitrous acid (ONOOH). One of the products of melatonin's interaction with H2O2, i.e., N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), is also a highly efficient radical scavenger. The cascade of reactions where the secondary metabolites are also effective scavenges is believed to contribute to melatonin's high efficacy in reducing oxidative damage. Besides its direct scavenging actions, melatonin stimulates several antioxidative enzymes including superoxide dismutase, glutathione peroxidase and glutathione reductase in addition to inhibiting a proxidative enzyme, nitric oxide synthase. This combination of actions assists melatonin in protecting cells from the degenerative changes normally associated with aging and age-related diseases.

Original languageEnglish (US)
Pages (from-to)1007-1019
Number of pages13
JournalMechanisms of Ageing and Development
Issue number8
StatePublished - Apr 30 2002


  • Aging
  • Free radicals
  • Melatonin
  • Nitrogen-based radicals
  • Oxygen-based radicals

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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