Analysis of N1-acetyl-N2-formyl-5-methoxykynuramine/ N1-acetyl-5-methoxy-kynuramine formation from melatonin in mice

Sida Niu, Feng Li, Dun Xian Tan, Lirong Zhang, Jeffrey R. Idle, Frank J. Gonzalez, Xiaochao Ma

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)106-114
Number of pages9
JournalJournal of Pineal Research
Volume49
Issue number2
DOIs
StatePublished - Sep 2010

Fingerprint

Kynuramine
Melatonin
Metabolomics
Urine
Oxidative Stress
Glucuronides
Acetaminophen
Feces
Mammals
Reactive Oxygen Species

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 journalArticle

Niu, Sida ; Li, Feng ; Tan, Dun Xian ; Zhang, Lirong ; Idle, Jeffrey R. ; Gonzalez, Frank J. ; Ma, Xiaochao. / Analysis of N1-acetyl-N2-formyl-5-methoxykynuramine/ N1-acetyl-5-methoxy-kynuramine formation from melatonin in mice. In: Journal of Pineal Research. 2010 ; Vol. 49, No. 2. pp. 106-114.
@article{7cc1cc258a004029bebd7352f622ced7,
title = "Analysis of N1-acetyl-N2-formyl-5-methoxykynuramine/ N1-acetyl-5-methoxy-kynuramine formation from melatonin in mice",
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.",
keywords = "antioxidant, melatonin, metabolism, N-acetyl-5-methoxy-kynuramine, N-acetyl-N-formyl-5-methoxykynuramine",
author = "Sida Niu and Feng Li and Tan, {Dun Xian} and Lirong Zhang and Idle, {Jeffrey R.} and Gonzalez, {Frank J.} and Xiaochao Ma",
year = "2010",
month = "9",
doi = "10.1111/j.1600-079X.2010.00771.x",
language = "English (US)",
volume = "49",
pages = "106--114",
journal = "Journal of Pineal Research",
issn = "0742-3098",
publisher = "Wiley-Blackwell",
number = "2",

}

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 -