Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Melatonin: an ancient molecule that makes oxygen metabolically tolerable

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. The effect of melatonin on endothelial dysfunction in patients after acute coronary syndrome: The MEFACS randomized clinical trial

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Utility of melatonin to treat surgical stress after major vascular surgery--a safety study.

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Pharmacokinetics of Melatonin: The Missing Link in Clinical Efficacy?

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Pharmacokinetics of high-dose intravenous melatonin in humans

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Pharmacokinetics of Alternative Administration Routes of Melatonin: A Systematic Review

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The Safety of Melatonin in Humans

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Melatonin as Protection Against Radiation Injury: A Systematic Review

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Lucien C Manchester
  • Ana Coto-Montes
  • Jose Antonio Boga
  • Lars Peter H Andersen
  • Zhou Zhou
  • Annia Galano
  • Jerry Vriend
  • Dun-Xian Tan
  • Russel J Reiter
View graph of relations

Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant, circadian rhythm regulator, anti-inflammatory and immunoregulating molecule, and as an oncostatic agent. We hypothesize that the initial and primary function of melatonin in photosynthetic cyanobacteria, which appeared on Earth 3.5-3.2 billion years ago, was as an antioxidant. The evolution of melatonin as an antioxidant by this organism was necessary as photosynthesis is associated with the generation of toxic-free radicals. The other secondary functions of melatonin came about much later in evolution. We also surmise that mitochondria and chloroplasts may be primary sites of melatonin synthesis in all eukaryotic cells that possess these organelles. This prediction is made on the basis that mitochondria and chloroplasts of eukaryotes developed from purple nonsulfur bacteria (which also produce melatonin) and cyanobacteria when they were engulfed by early eukaryotes. Thus, we speculate that the melatonin-synthesizing actions of the engulfed bacteria were retained when these organelles became mitochondria and chloroplasts, respectively. That mitochondria are likely sites of melatonin formation is supported by the observation that this organelle contains high levels of melatonin that are not impacted by blood melatonin concentrations. Melatonin has a remarkable array of means by which it thwarts oxidative damage. It, as well as its metabolites, is differentially effective in scavenging a variety of reactive oxygen and reactive nitrogen species. Moreover, melatonin and its metabolites modulate a large number of antioxidative and pro-oxidative enzymes, leading to a reduction in oxidative damage. The actions of melatonin on radical metabolizing/producing enzymes may be mediated by the Keap1-Nrf2-ARE pathway. Beyond its direct free radical scavenging and indirect antioxidant effects, melatonin has a variety of physiological and metabolic advantages that may enhance its ability to limit oxidative stress.

Original languageEnglish
JournalJournal of Pineal Research
Volume59
Issue number4
Pages (from-to)403-19
Number of pages17
ISSN0742-3098
DOIs
Publication statusPublished - Nov 2015

ID: 46000472