RT Journal Article
SR Electronic
T1 Pharmacokinetics and Metabolism of Hydroxytyrosol, a Natural Antioxidant from Olive Oil
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1492
OP 1498
VO 29
IS 11
A1 D'Angelo, Stefania
A1 Manna, Caterina
A1 Migliardi, Valentina
A1 Mazzoni, Orazio
A1 Morrica, Patrizia
A1 Capasso, Giovanni
A1 Pontoni, Gabriele
A1 Galletti, Patrizia
A1 Zappia, Vincenzo
YR 2001
UL http://dmd.aspetjournals.org/content/29/11/1492.abstract
AB 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