Evaluation of the Bioavailability and Metabolism of Nitroderivatives of Hydroxytyrosol Using Caco-2 and HepG2 Human Cell Models

详细信息    查看全文

• 作者：Elena Gallardo ; Beatriz Sarria ; José Luis Espartero ; José Antonio Gonzalez Correa ; Laura Bravo-Clemente ; Raquel Mateos
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2016
• 出版时间：March 23, 2016
• 年：2016
• 卷：64
• 期：11
• 页码：2289-2297
• 全文大小：430K
• ISSN：1520-5118

文摘

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.