Evaluation of the bioavailability and metabolism of nitroderivatives of hydroxytyrosol Using Caco-2 and HepG2 human cell models
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 (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.
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American Chemical Society
2016
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Subjects: | Parkinson’s disease, Metabolism, Nitrocatechols, Hydroxytyrosol, Bioavailability, |
Online Access: | http://hdl.handle.net/10261/171540 http://dx.doi.org/10.13039/501100011011 |
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dig-ictan-es-10261-1715402020-12-10T16:15:50Z Evaluation of the bioavailability and metabolism of nitroderivatives of hydroxytyrosol Using Caco-2 and HepG2 human cell models Gallardo, Elena Sarriá, Beatriz Espartero, José L. González Correa, José A. Bravo, Laura Mateos, Raquel Junta de Andalucía Parkinson’s disease Metabolism Nitrocatechols Hydroxytyrosol Bioavailability 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 (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. This work was supported by Grant P09-AGR-5098 from Junta de Andalucía (Spain). E.G. thanks Junta de Andalucia for a predoctoral fellowship. Peer Reviewed 2018-10-25T07:25:04Z 2018-10-25T07:25:04Z 2016 2018-10-25T07:25:04Z artículo http://purl.org/coar/resource_type/c_6501 doi: 10.1021/acs.jafc.6b00401 e-issn: 1520-5118 issn: 0021-8561 Journal of Agricultural and Food Chemistry 64(11): 2289-2297 (2016) http://hdl.handle.net/10261/171540 10.1021/acs.jafc.6b00401 http://dx.doi.org/10.13039/501100011011 26915652 Postprint https://doi.org/10.1021/acs.jafc.6b00401 Sí open American Chemical Society |
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Parkinson’s disease Metabolism Nitrocatechols Hydroxytyrosol Bioavailability Parkinson’s disease Metabolism Nitrocatechols Hydroxytyrosol Bioavailability |
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Parkinson’s disease Metabolism Nitrocatechols Hydroxytyrosol Bioavailability Parkinson’s disease Metabolism Nitrocatechols Hydroxytyrosol Bioavailability Gallardo, Elena Sarriá, Beatriz Espartero, José L. González Correa, José A. Bravo, Laura Mateos, Raquel Evaluation of the bioavailability and metabolism of nitroderivatives of hydroxytyrosol Using Caco-2 and HepG2 human cell models |
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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 (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. |
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Junta de Andalucía |
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Junta de Andalucía Gallardo, Elena Sarriá, Beatriz Espartero, José L. González Correa, José A. Bravo, Laura Mateos, Raquel |
format |
artículo |
topic_facet |
Parkinson’s disease Metabolism Nitrocatechols Hydroxytyrosol Bioavailability |
author |
Gallardo, Elena Sarriá, Beatriz Espartero, José L. González Correa, José A. Bravo, Laura Mateos, Raquel |
author_sort |
Gallardo, Elena |
title |
Evaluation of the bioavailability and metabolism of nitroderivatives of hydroxytyrosol Using Caco-2 and HepG2 human cell models |
title_short |
Evaluation of the bioavailability and metabolism of nitroderivatives of hydroxytyrosol Using Caco-2 and HepG2 human cell models |
title_full |
Evaluation of the bioavailability and metabolism of nitroderivatives of hydroxytyrosol Using Caco-2 and HepG2 human cell models |
title_fullStr |
Evaluation of the bioavailability and metabolism of nitroderivatives of hydroxytyrosol Using Caco-2 and HepG2 human cell models |
title_full_unstemmed |
Evaluation of the bioavailability and metabolism of nitroderivatives of hydroxytyrosol Using Caco-2 and HepG2 human cell models |
title_sort |
evaluation of the bioavailability and metabolism of nitroderivatives of hydroxytyrosol using caco-2 and hepg2 human cell models |
publisher |
American Chemical Society |
publishDate |
2016 |
url |
http://hdl.handle.net/10261/171540 http://dx.doi.org/10.13039/501100011011 |
work_keys_str_mv |
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1777670582042624000 |