TY - JOUR T1 - Pharmacokinetics and Metabolism of Hydroxytyrosol, a Natural Antioxidant from Olive Oil JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1492 LP - 1498 VL - 29 IS - 11 AU - Stefania D'Angelo AU - Caterina Manna AU - Valentina Migliardi AU - Orazio Mazzoni AU - Patrizia Morrica AU - Giovanni Capasso AU - Gabriele Pontoni AU - Patrizia Galletti AU - Vincenzo Zappia Y1 - 2001/11/01 UR - http://dmd.aspetjournals.org/content/29/11/1492.abstract N2 - 3,4-Dihydroxyphenylethanol (DOPET) is the majoro-diphenol detectable in extra virgin olive oil, either in free or esterified form. Despite its relevant biological effects, mainly related to its antioxidant properties, little data have been reported so far on its toxicity and metabolism. The aim of the present work is to evaluate DOPET toxicity and to investigate its molecular pharmacokinetics by using the 14C-labeled diphenol. When orally administered to rats, the molecule does not show appreciable toxicity up to 2 g/kg b.wt. To identify and quantify its metabolites, [14C]DOPET has been synthesized and intravenously injected in rats. The pharmacokinetic analysis indicates a fast and extensive uptake of the molecule by the organs and tissues investigated, with a preferential renal uptake. Moreover, 90% of the administered radioactivity is excreted in urine collected up to 5 h after injection, and about 5% is detectable in feces and gastrointestinal content. The characterization of the labeled metabolites, extracted from the organs and urine, has been performed by high-pressure liquid chromatography analysis. In all the investigated tissues, DOPET is enzymatically converted in four oxidized and/or methylated derivatives. Moreover, a significant fraction of total radioactivity is associated with the sulfo-conjugated forms, which also represent the major urinary excretion products. On the basis of the reported results, an intracellular metabolic pathway of exogenously administered DOPET, implying the involvement of catechol-O-methyltransferase, alcohol dehydrogenase, aldehyde dehydrogenase, and phenolsulfotransferase, has been proposed. The American Society for Pharmacology and Experimental Therapeutics ER -