TY - JOUR
T1 - A novel melatonin metabolite, cyclic 3-hydroxymelatonin
T2 - A biomarker of in vivo hydroxyl radical generation
AU - Tan, Dun-xian
AU - Manchester, Lucien C.
AU - Reiter, Russel J.
AU - Plummer, Benjamin F.
AU - Hardies, Lou J.
AU - Weintraub, Susan T.
AU - Vijayalaxmi, Unknown
AU - Shepherd, Alexander M.M.
PY - 1998/12/30
Y1 - 1998/12/30
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1998.9826
DO - 10.1006/bbrc.1998.9826
M3 - Article
C2 - 9918777
AN - SCOPUS:0032583461
SN - 0006-291X
VL - 253
SP - 614
EP - 620
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -