title: Tissue distribution and metabolism of the putative cancer chemopreventive agent 3',4',5'-trimethoxyflavonol (TMFol) in mice.
abstract: 3',4',5'-Trimethoxyflavonol (TMFol) is a synthetic flavonol with preclinical cancer chemopreventive properties. The hypothesis was tested that, in mice, p.o. administration of TMFol results in measureable levels of the parent in target tissues. A single oral dose (240 mg/kg) was administered to mice (n = 4 per time point) with time points ranging from 5 to 1440 min. TMFol and its metabolites were identified and quantitated in all tissues by high-performance liquid chromatography (HPLC). Plasma levels of TMFol were at the limit of quantification or below, although metabolites were identified. Peak levels of TMFol in the gastrointestinal tract and the prostate averaged 1671 ± 265 µg/g (5.3 µmol/g) and 6.0 ± 1.6 µg/g (18.4 nmol/g), and occurred 20 and 360 min post-dose, respectively. The area under the tissue concentration-time curve (AUC) for TMFol was greater than those of the metabolites, indicating that TMFol is relatively metabolically stable. Micromolar TMFol levels are easily achieved in the prostate and gastrointestinal tract, suggesting that TMFol might exert chemopreventive efficacy at these tissue sites. Further investigations are warranted to elucidate the potential chemopreventive potency of TMFol.
authors.affiliation: Department of Cancer Studies and Molecular Medicine, RKCSB, Leicester Royal Infirmary, University of Leicester, Leicester LE2 7LX, UK.
authors.forename: Shaban E A
authors.initials: SE
authors.lastname: Saad
authors.forename: Donald J L
authors.initials: DJ
authors.lastname: Jones
authors.forename: Leonie M
authors.initials: LM
authors.lastname: Norris
authors.forename: Emma
authors.initials: E
authors.lastname: Horner-Glister
authors.forename: Ketan R
authors.initials: KR
authors.lastname: Patel
authors.forename: Robert G
authors.initials: RG
authors.lastname: Britton
authors.forename: William P
authors.initials: WP
authors.lastname: Steward
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Gescher
authors.forename: Karen
authors.initials: K
authors.lastname: Brown
authors.forename: Stewart
authors.initials: S
authors.lastname: Sale
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000032:analysis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D005419:Flavonoids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D044948:Flavonols / Q000032:analysis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D008810:Mice, Inbred C57BL; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: C578455:3',4',5'-trimethoxyflavonol; D016588:Anticarcinogenic Agents; D005419:Flavonoids; D044948:Flavonols; C441202:3',4',5'-trimethoxyflavone