Pharmacology and physiology of melatonin in the reduction of oxidative stress in vivo

Russel J. Reiter, Dun-Xian Tan, Wenbo Qi, Lucien C. Manchester, Malgorzata Karbownik, Juan R. Calvo

Research output: Contribution to journalArticlepeer-review

259 Scopus citations


This brief resume summarizes the evidence which shows that melatonin is a significant free radical scavenger and antioxidant at both physiological and pharmacological concentrations in vivo. Surgical removal of the pineal gland, a procedure which lowers endogenous melatonin levels in the blood, exaggerates molecular damage due to free radicals during an oxidative challenge. Likewise, providing supplemental melatonin during periods of massive free radical production greatly lowers the resulting tissue damage and dysfunction. In the current review, these findings are considered in terms of neurodegenerative diseases, cancer, ischemia/reperfusion injury and aging. Besides being a highly effective direct free radical scavenger and indirect antioxidant, melatonin has several features that make it of clinical interest. Thus, melatonin is readily absorbed when it is administered via any route, it crosses all morphophysiological barriers, e.g., blood-brain barrier and placenta, with ease, it seems to enter all parts of every cell where it prevents oxidative damage, it preserves mitochondrial function, and it has low toxicity. While blood melatonin levels are normally low, tissue levels of the indoleamine can be considerably higher and at some sites, e.g., in bone marrow cells and bile, melatonin concentrations exceed those in the blood by several orders of magnitude. What constitutes a physiological level of melatonin must be redefined in terms of the bodily fluid, tissue and subcellular compartment being examined.

Original languageEnglish (US)
Pages (from-to)160-171
Number of pages12
Issue number3-4
StatePublished - Jul 20 2000


  • Antioxidant
  • Cancer
  • Free radicals
  • Ischemia/reperfusion injury
  • Melatonin
  • Neurogeneration

ASJC Scopus subject areas

  • General Medicine


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