A novel melatonin metabolite, cyclic 3-hydroxymelatonin: A biomarker of in vivo hydroxyl radical generation

Dun-xian Tan, Lucien C. Manchester, Russel J. Reiter, Benjamin F. Plummer, Lou J. Hardies, Susan T. Weintraub, Unknown Vijayalaxmi, Alexander M.M. Shepherd

Research output: Contribution to journalArticlepeer-review

349 Scopus citations


In the current study, we characterized a urinary melatonin metabolite which could provide a safe and effective method to monitor generation of HO(·) in humans. Using mass spectrometry (MS), proton nuclear magnetic resonance (1H NMR), COSY 1H NMR analysis, and calculations on the relative thermodynamic stability, a novel melatonin metabolite was identified as cyclic 3-hydroxymelatonin (3-OHM). 3-OHM is the product of the reaction of melatonin with HO(·) which was generated in two different cell-free in vitro systems. Interestingly, this same metabolite, 3-OHM, was also identified in the urine of both rats and humans. A proposed reaction pathway suggests that 3-OHM is the footprint product that results when a melatonin molecule scavenges two HO(·). When rats were challenged with ionizing radiation which results in HO(·) generation, urinary 3-OHM increased dramatically compared to that of controls. These results strongly indicate that the quantity of 3-OHM produced is associated with in vivo HO(·) generation. Since melatonin exists in virtually all animal species and has a wide intracellular distribution and 3-OHM is readily detected noninvasively in urine, we suggest that 3-OHM is a valuable biomarker that can be used to monitor in vivo HO(·) levels in humans and other species. The measurement of urinary 3-OHM as a biomarker of HO(·) generation could provide clinical benefits in the diagnosis and treatment of diseases.

Original languageEnglish (US)
Pages (from-to)614-620
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Dec 30 1998

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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