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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Jacobs, H. Koek, G. H. Peters, R. Moalin, M. Tack, J. Van Der Vijgh, W. J. Bast, A. Haenen, G. R. |
| Description | Country affiliation: Netherlands Author Affiliation: Jacobs H ( Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands. hilde.jacobs@maastrichtuniversity.nl) |
| Abstract | Despite its well-known cardiotoxicity, the anthracycline doxorubicin continues to be a widely used chemotherapeutic agent. The flavonoid 7-mono-O-(ß-hydroxyethyl)-rutoside (monoHER) has shown protection against doxorubicin-induced cardiotoxicity in mice. However, this protection has not been observed in humans. This prompted us to investigate monoHER metabolism in humans and compare it with that in mice. Five healthy volunteers received monoHER by intravenous infusion. After infusion, bile fluid was collected, and the monoHER metabolites were identified by liquid chromatography-diode-array detection (LC-DAD), time-of-flight mass spectrometry (TOF-MS), and (1)H-nuclear magnetic resonance (NMR). Thirteen different metabolites were identified. MonoHER was predominantly converted into inactive glucuronidated metabolites. In mice, the major metabolic route is methylation, which forms bioactive metabolites that are implicated in the cardioprotective effect of monoHER. This indicates that the different pharmacological effects of monoHER in mice and humans might be explained by a difference in monoHER metabolism. This study adds to the growing appreciation of flavonoid metabolites as bioactive compounds. |
| File Format | HTM / HTML |
| ISSN | 00099236 |
| Issue Number | 6 |
| Volume Number | 90 |
| e-ISSN | 15326535 |
| Journal | Clinical Pharmacology & Therapeutics |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2011-12-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Pharmacology Antioxidants Metabolism Glucuronides Hydroxyethylrutoside Analogs & Derivatives Methylation Adult Animals Pharmacology Bile Chromatography, Liquid Methods Female Humans Infusions, Intravenous Magnetic Resonance Spectroscopy Male Mass Spectrometry Mice Species Specificity Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
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