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Evaluation of the bioavailability and metabolism of nitroderivatives of hydroxytyrosol Using Caco-2 and HepG2 human cell models

AuthorsGallardo, Elena; Sarriá, Beatriz ; Espartero, José L.; González Correa, José A.; Bravo, Laura ; Mateos, Raquel
KeywordsParkinson’s disease
Issue Date2016
PublisherAmerican Chemical Society
CitationJournal of Agricultural and Food Chemistry 64(11): 2289-2297 (2016)
AbstractConsidering 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 (NOHT), nitrohydroxytyrosyl acetate (NOHT-A), and ethyl nitrohydroxytyrosyl ether (NOHT-E) were efficiently transferred across human Caco-2 cell monolayers as an intestinal barrier model, NOHT-A and NOHT-E being better (p < 0.05) absorbed (absorption rate (AR) = 1.4 ± 0.1 and 1.5 ± 0.2, respectively) than their precursor, NOHT (AR = 1.1 ± 0.1). A significant amount of the absorbed compounds remained unconjugated (81, 70, and 33% for NOHT, NOHT-A, and NOHT-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 NOHT-A into NOHT, whereas NOHT-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, NOHT, NOHT-A, and NOHT-E show high in vitro bioavailability and are extensively metabolized by hepatic cells.
Publisher version (URL)https://doi.org/10.1021/acs.jafc.6b00401
Identifiersdoi: 10.1021/acs.jafc.6b00401
e-issn: 1520-5118
issn: 0021-8561
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