Abstract
The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N 1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N 1-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 106-114 |
| Number of pages | 9 |
| Journal | Journal of Pineal Research |
| Volume | 49 |
| Issue number | 2 |
| DOIs | |
| State | Published - Sep 2010 |
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Keywords
- antioxidant
- melatonin
- metabolism
- N-acetyl-5-methoxy-kynuramine
- N-acetyl-N-formyl-5-methoxykynuramine
ASJC Scopus subject areas
- Endocrinology
Cite this
Analysis of N1-acetyl-N2-formyl-5-methoxykynuramine/ N1-acetyl-5-methoxy-kynuramine formation from melatonin in mice. / Niu, Sida; Li, Feng; Tan, Dun Xian; Zhang, Lirong; Idle, Jeffrey R.; Gonzalez, Frank J.; Ma, Xiaochao.
In: Journal of Pineal Research, Vol. 49, No. 2, 09.2010, p. 106-114.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Analysis of N1-acetyl-N2-formyl-5-methoxykynuramine/ N1-acetyl-5-methoxy-kynuramine formation from melatonin in mice
AU - Niu, Sida
AU - Li, Feng
AU - Tan, Dun Xian
AU - Zhang, Lirong
AU - Idle, Jeffrey R.
AU - Gonzalez, Frank J.
AU - Ma, Xiaochao
PY - 2010/9
Y1 - 2010/9
N2 - The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N 1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N 1-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.
AB - The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N 1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N 1-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.
KW - antioxidant
KW - melatonin
KW - metabolism
KW - N-acetyl-5-methoxy-kynuramine
KW - N-acetyl-N-formyl-5-methoxykynuramine
UR - http://www.scopus.com/inward/record.url?scp=77955140547&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955140547&partnerID=8YFLogxK
U2 - 10.1111/j.1600-079X.2010.00771.x
DO - 10.1111/j.1600-079X.2010.00771.x
M3 - Article
VL - 49
SP - 106
EP - 114
JO - Journal of Pineal Research
JF - Journal of Pineal Research
SN - 0742-3098
IS - 2
ER -