Sida Niu and Feng Li contribute equally to this study.
Analysis of N1-acetyl-N2-formyl-5-methoxykynuramine/N1-acetyl-5-methoxy-kynuramine formation from melatonin in mice
Article first published online: 27 MAY 2010
© 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S
Journal of Pineal Research
Volume 49, Issue 2, pages 106–114, September 2010
How to Cite
Niu, S., Li, F., Tan, D.-X., Zhang, L., Idle, J. R., Gonzalez, F. J. and Ma, X. (2010), Analysis of N1-acetyl-N2-formyl-5-methoxykynuramine/N1-acetyl-5-methoxy-kynuramine formation from melatonin in mice. Journal of Pineal Research, 49: 106–114. doi: 10.1111/j.1600-079X.2010.00771.x
This work was supported by the National Institutes of Health National Center for Research Resources [COBRE 5P20-RR021940]. Jeffrey R. Idle is grateful to US Smokeless Tobacco Company for a collaborative research grant.
- Issue published online: 2 AUG 2010
- Article first published online: 27 MAY 2010
- Received December 9, 2009; accepted March 18, 2010.
Abstract: The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxy-kynuramine (AMK). The physiological or pathological significance of AFMK/AMK formation during the process of melatonin metabolism in mammals has not been clarified. Using a metabolomic approach in the current study, the AFMK/AMK pathway was thoroughly investigated both in mice and humans. Unexpectedly, AFMK and AMK were not identified in the urine of humans nor in the urine, feces or tissues (including liver, brain, and eyes) in mice under the current experimental conditions. Metabolomic analysis did identify novel metabolites of AMK, i.e. hydroxy-AMK and glucuronide-conjugated hydroxy-AMK. These two newly identified metabolites were, however, not found in the urine of humans. In addition, oxidative stress induced by acetaminophen in the mouse model did not boost AFMK/AMK formation. These data suggest that AFMK/AMK formation is not a significant pathway of melatonin disposition in mice, even under conditions of oxidative stress.