title: Dose effect on the uptake and accumulation of hydroxytyrosol and its metabolites in target tissues in rats.
abstract: Hydroxytyrosol (HT) is the most prominent phenolic compound of virgin olive oil and due to its scientifically validated biological activities it is entering to the market as a potentially useful supplement for cardiovascular disease prevention. The aim of the present study was to investigate the relationship between the HT dose intake and its tissue uptake in rats, and thus, providing complementary information in relation to the target-dose relationship. Rats were given a refined olive oil enriched with HT at different doses (1, 10, and 100 mg/kg) and they were sacrificed after 5 h to ensure the cell tissue uptake of HT and its metabolites. Plasma samples and different organs as liver, kidney, heart and brain were obtained, and HT metabolites were analyzed by UPLC-MS/MS. The results showed that HT and its metabolites could be accumulated in a dose-dependent manner basically in the liver, kidney, and brain and were detected in these tissues even at nutritionally relevant human doses. The detection of free HT in liver and kidney was noteworthy. To date, this appears to be the only biologically active form, and thus, it provides relevant information for optimizing the potential applications of HT to prevent certain hepatic and renal diseases. In recent years, HT and its derivatives have led to a great interest from the virgin olive oil producers and manufacturers of nutraceutical supplements. The increasing interest in HT is mainly due to the European Food Safety Agency (EFSA) Panel on Dietetic Products, Nutrition, and Allergies (NDA) scientific opinion that established a cause-and-effect relationship between the consumption of olive oil polyphenols and protection of LDL particles from oxidative damage . Based on this positive opinion, the health claim "Olive oil polyphenols contribute to the protection of blood lipids from oxidative stress" was included in the list of health claims , being the only authorized health claim in the European Union regarding polyphenols and health.
authors: Food Technology Department, Agrotecnio Research Center, Escuela Técnica Superior de Ingeniería Agraria, University of Lleida, Lleida, Spain.
authors: Maria-Carmen
authors: MC
authors: López de las Hazas
authors: Food Technology Department, Agrotecnio Research Center, Escuela Técnica Superior de Ingeniería Agraria, University of Lleida, Lleida, Spain.
authors: Laura
authors: L
authors: Rubió
authors: Human Pharmacology and Clinical Neurociences Research Group, IMIM-Institut, Hospital del Mar d'Investigaciones Mèdiques, Barcelona, Spain.|Pompeu Fabra University (CEXS-UPF), Barcelona, Spain.
authors: Aristotelis
authors: A
authors: Kotronoulas
authors: Human Pharmacology and Clinical Neurociences Research Group, IMIM-Institut, Hospital del Mar d'Investigaciones Mèdiques, Barcelona, Spain.|Cardiovascular Risk and Nutrition Research Group, REGICOR Study Group, IMIM-Research Institute Hospital del Mar, Barcelona, Spain.
authors: Rafael
authors: R
authors: de la Torre
authors: Unitat de Recerca en Lípids i Arteriosclerosis, CIBERDEM, St. Joan de Reus University Hospital, IISPV, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Spain.
authors: Rosa
authors: R
authors: Solà
authors: Food Technology Department, Agrotecnio Research Center, Escuela Técnica Superior de Ingeniería Agraria, University of Lleida, Lleida, Spain.
authors: Maria-José
authors: MJ
authors: Motilva
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D000069463:Olive Oil; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D000069463:Olive Oil; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol
keywords: Biodistribution; Dose-uptake; Hydroxytyrosol; Phenol metabolites; Tissue disposition