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Accumulation and metabolism of the anticancer flavonoid 5,7-dimethoxyflavone compared to its unmethylated analog chrysin in the Atlantic killifish.

Abstract
The use of dietary flavonoids as potential chemopreventive agents is a concept of increasing interest. Recent findings indicate that methylated flavones have the advantage of increased metabolic stability. One such compound, the naturally-occurring 5,7-dimethoxyflavone (5,7-DMF), has been shown to be a potential chemopreventive agent in human cancer originating from the liver, mouth, esophagus and lung. As bioavailability is a key issue for potential in vivo effects, the tissue accumulation and biliary elimination of 5,7-DMF and its non-methylated analog chrysin were examined in a small fish model (Fundulus heteroclitus). The fish were exposed to 5,7-DMF, chrysin or vehicle control (DMSO<0.01%) in seawater for 8h. Toxicity was not observed at the 5microM exposure level. Tissues and bile were harvested and analyzed by HPLC and LC/MS for quantitation and identification of parent compound and metabolites. 5,7-DMF accumulated 20-fold to 100-fold in all tissues examined, with the highest accumulation in liver and brain, whereas chrysin was barely detectable in any tissues except the liver. The bile of chrysin-exposed fish contained very low concentrations of unchanged chrysin but high concentrations of two glucuronic acid conjugates. In the bile of 5,7-DMF-exposed fish, the parent compound was detectable in significant amounts along with glucuronic acid conjugates of O-demethylated 5,7-DMF. In conclusion, our study demonstrated high tissue accumulation and limited metabolism of 5,7-DMF compared to chrysin in vivo, making this flavone a promising chemopreventive molecule.
AuthorsPetra A Tsuji, Richard N Winn, Thomas Walle
JournalChemico-biological interactions (Chem Biol Interact) Vol. 164 Issue 1-2 Pg. 85-92 (Dec 01 2006) ISSN: 0009-2797 [Print] Ireland
PMID16999945 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Anticarcinogenic Agents
  • Flavonoids
  • 5,7-dimethoxyflavone
  • chrysin
  • Glucuronic Acid
  • Dimethyl Sulfoxide
Topics
  • Animals
  • Anticarcinogenic Agents (pharmacology)
  • Bile (metabolism)
  • Brain (metabolism)
  • Chromatography, High Pressure Liquid
  • Dimethyl Sulfoxide (metabolism)
  • Dose-Response Relationship, Drug
  • Flavonoids (metabolism)
  • Glucuronic Acid (metabolism)
  • Humans
  • Killifishes (metabolism)
  • Liver (metabolism)
  • Mass Spectrometry
  • Methylation
  • Seawater
  • Time Factors
  • Tissue Distribution

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