PMID- 21266594
OWN - NLM
STAT- MEDLINE
DCOM- 20111230
LR  - 20131121
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Linking)
VI  - 39
IP  - 5
DP  - 2011 May
TI  - Identification of the metabolites of the antioxidant flavonoid 
      7-mono-O-(beta-hydroxyethyl)-rutoside in mice.
PG  - 750-6
LID - 10.1124/dmd.110.036525 [doi]
AB  - The clinical use of the anticancer drug doxorubicin is limited by severe 
      cardiotoxicity. In mice, the semisynthetic antioxidant flavonoid 
      7-mono-O-(beta-hydroxyethyl)-rutoside (monoHER) has been successfully used as a 
      protector against doxorubicin-induced cardiotoxicity. However, most monoHER has 
      already been cleared from the body at the time that doxorubicin concentrations 
      are still high. This result suggests that not only the parent compound monoHER 
      itself but also monoHER metabolites could be responsible for the observed 
      cardioprotective effects in mice. Therefore, in the present study, we 
      investigated the metabolism of monoHER in mice. Mice were administered 500 mg/kg 
      monoHER intraperitoneally. At different time points after monoHER administration, 
      bile was collected and analyzed for the presence of monoHER metabolites. The 
      formed metabolites were identified by liquid chromatography-diode array 
      detection-time of flight-mass spectrometry. Thirteen different metabolites were 
      identified. The observed routes of monoHER metabolism are methylation, 
      glucuronidation, oxidation of its hydroxyethyl group, GSH conjugation, and 
      hydrolysis of its disaccharide. In line with other flavonoids, methylated monoHER 
      and the monoHER glucosides are expected to have relatively high cellular uptake 
      and low clearance from the body. Therefore, these metabolites might contribute to 
      the observed protection of monoHER against doxorubicin-induced cardiotoxicity.
FAU - Jacobs, Hilde
AU  - Jacobs H
AD  - Department of Pharmacology and Toxicology, NUTRIM School for Nutrition, 
      Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The 
      Netherlands. hilde.jacobs@maastrichtuniversity.nl
FAU - Peters, Ron
AU  - Peters R
FAU - den Hartog, Gertjan J M
AU  - den Hartog GJ
FAU - van der Vijgh, Wim J F
AU  - van der Vijgh WJ
FAU - Bast, Aalt
AU  - Bast A
FAU - Haenen, Guido R M M
AU  - Haenen GR
LA  - eng
PT  - Journal Article
DEP - 20110125
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (7-monohydroxyethylrutoside)
RN  - 0 (Antioxidants)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Glucuronides)
RN  - 0 (Hydroxyethylrutoside)
RN  - 80168379AG (Doxorubicin)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Antioxidants/analysis/*chemistry/*metabolism/pharmacology
MH  - Bile/*metabolism
MH  - Cardiotonic Agents/chemistry/*metabolism/pharmacology
MH  - Doxorubicin/toxicity
MH  - Glucuronides/chemistry/metabolism
MH  - Glutathione/chemistry/metabolism
MH  - Hydroxyethylrutoside/*analogs & derivatives/chemistry/metabolism/pharmacology
MH  - Male
MH  - Methylation
MH  - Mice
MH  - Mice, Inbred BALB C
EDAT- 2011/01/27 06:00
MHDA- 2011/12/31 06:00
CRDT- 2011/01/27 06:00
PHST- 2011/01/27 06:00 [entrez]
PHST- 2011/01/27 06:00 [pubmed]
PHST- 2011/12/31 06:00 [medline]
AID - dmd.110.036525 [pii]
AID - 10.1124/dmd.110.036525 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2011 May;39(5):750-6. doi: 10.1124/dmd.110.036525. Epub 2011 
      Jan 25.