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

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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-12, Vol.253 (3), p.614-620
Main Authors: Tan, D X, Manchester, L C, Reiter, R J, Plummer, B F, Hardies, L J, Weintraub, S T, Vijayalaxmi, Shepherd, A M
Format: Article
Language:English
Subjects:
Animals
Biomarkers
Free Radical Scavengers - metabolism
Free Radicals - metabolism
Humans
Hydroxyl Radical - metabolism
Male
Mass Spectrometry
Melatonin - analogs & derivatives
Melatonin - metabolism
Melatonin - urine
Nuclear Magnetic Resonance, Biomolecular
Rats
Rats, Sprague-Dawley
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Summary: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.
ISSN:0006-291X
DOI:10.1006/bbrc.1998.9826