title: Tissue distribution of rat flavanol metabolites at different doses.
abstract: Flavanols are metabolized in the small intestine and the liver to produce their glucuronidated, sulfated or methylated conjugates that can be body distributed or excreted in the urine. However, the intake of large amounts of flavanols is not directly related to their bioavailability. This study aims to investigate the administered dose dependence of flavanols' conjugation and body distribution. In this study, different doses of a grape seed proanthocyanidin extract (GSPE; 125, 250, 375 and 1000 mg/kg) were orally administered to male Wistar rats. Tissues were collected 2h after GSPE administration. Flavanols were quantified by HPLC-MS/MS. Results show that the majority of GSPE metabolites are located in the kidney, followed by the liver. Lower concentrations were found in mesenteric white adipose tissue (MWAT) and the brain. Moreover, flavanol metabolites followed a tissue-specific distribution pattern independent of dosage. In the kidney, glucuronidated metabolites were the most abundant; however, in the liver, it was mainly methyl-glucuronidated metabolites. In MWAT, free flavanols were dominant, and methylated metabolites were dominant in the brain. Concentration within a tissue was dependent on the administered dose. In conclusion, flavanol metabolites follow a tissue-specific distribution pattern and only the tissue concentration of flavanol metabolites is dependent on the administered dose.
authors.affiliation: Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007 Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Margalef
authors.affiliation: Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007 Spain.
authors.forename: Zara
authors.initials: Z
authors.lastname: Pons
authors.affiliation: Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007 Spain.
authors.forename: Francisca Isabel
authors.initials: FI
authors.lastname: Bravo
authors.affiliation: Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007 Spain; Technological Center of Nutrition and Health (CTNS), TECNIO, CEICS, Reus 43204, Spain. Electronic address: begona.muguerza@urv.cat.
authors.forename: Begoña
authors.initials: B
authors.lastname: Muguerza
authors.affiliation: Nutrigenomic Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona 43007 Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Arola-Arnal
mesh_terms: D052436:Adipose Tissue, White / Q000737:chemistry; D000818:Animals; D001682:Biological Availability; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D044948:Flavonols / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D020719:Glucuronides / Q000032:analysis; D056604:Grape Seed Extract / Q000008:administration & dosage; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008297:Male; D008643:Mesentery / Q000737:chemistry; D008745:Methylation; D044945:Proanthocyanidins / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D044948:Flavonols; D020719:Glucuronides; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins
keywords: Brain; Grape seed extract; HPLC–MS/MS; Mesenteric white adipose tissue; Proanthocyanidins