title: Evaluation of the Bioavailability and Metabolism of Nitroderivatives of Hydroxytyrosol Using Caco-2 and HepG2 Human Cell Models.
abstract: Considering that nitrocatechols present putative effects against Parkinson's disease, the absorption and metabolism of nitroderivatives of hydroxytyrosol (HT) were assessed using human cell model systems. The test compounds nitrohydroxytyrosol (NO2HT), nitrohydroxytyrosyl acetate (NO2HT-A), and ethyl nitrohydroxytyrosyl ether (NO2HT-E) were efficiently transferred across human Caco-2 cell monolayers as an intestinal barrier model, NO2HT-A and NO2HT-E being better (p < 0.05) absorbed (absorption rate (AR) = 1.4 ± 0.1 and 1.5 ± 0.2, respectively) than their precursor, NO2HT (AR = 1.1 ± 0.1). A significant amount of the absorbed compounds remained unconjugated (81, 70, and 33% for NO2HT, NO2HT-A, and NO2HT-E, respectively) after incubation in Caco-2 cells, being available for hepatic metabolism. Nitrocatechols were extensively taken up and metabolized by human hepatoma HepG2 cells as a model of the human liver. Both studies revealed extensive hydrolysis of NO2HT-A into NO2HT, whereas NO2HT-E was not hydrolyzed. Glucuronide (75-55%), methylglucuronide (25-33%), and methyl derivatives (0-12%) were the main nitrocatechol metabolites detected after metabolism in Caco-2 and HepG2 cells. In conclusion, NO2HT, NO2HT-A, and NO2HT-E show high in vitro bioavailability and are extensively metabolized by hepatic cells.
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), CSIC , Madrid, Spain.|Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, Seville, Spain.|Department of Pharmacology and Therapeutics, School of Medicine, University of Malaga , Malaga, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Gallardo
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), CSIC , Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sarria
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, Seville, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Espartero
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, University of Malaga , Malaga, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Gonzalez Correa
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), CSIC , Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo-Clemente
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), CSIC , Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Mateos
mesh_terms: D001682:Biological Availability; D018938:Caco-2 Cells; D056945:Hep G2 Cells; D006801:Humans; D006868:Hydrolysis; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological; D009574:Nitro Compounds / Q000378:metabolism* / Q000493:pharmacokinetics*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D009574:Nitro Compounds; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol
keywords: Parkinson’s disease; bioavailability; hydroxytyrosol; metabolism; nitrocatechols