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Gender differences in plasma and urine metabolites from Sprague–Dawley rats after oral administration of normal and high doses of hydroxytyrosol, hydroxytyrosol acetate, and DOPAC

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Abstract

Purpose

To date, several in vitro and in vivo studies have shown phenolic compounds occurring naturally in olives and olive oil to be beneficial to human health due to their interaction with intracellular signaling pathways. However, the bioavailability of the most important of these compounds, hydroxytyrosol (HT), and its transformation into derivatives within the organism after oral intake are still not completely understood, requiring further in vivo research. This study deals with the differential bioavailability and metabolism of oral HT and its derivatives in rats.

Methods

Hydroxytyrosol (HT), hydroxytyrosol acetate (HTA), and 2,3-dihydroxyphenylacetic acid (DOPAC) were administered at doses of 1 and 5 mg/kg to Sprague–Dawley rats (n = 9 per treatment) by oral gavage. Their plasma kinetics and absorption ratio, assessed as their excretion in 24-h urine, were determined by UHPLC/MS/MS.

Results

Plasma and urine levels indicated that although the three compounds are efficiently absorbed in the gastrointestinal tract and show similar metabolism, the bioavailability is strongly dependent on the derivative considered, dosage, and gender. Inter-conversion among them has been described also, suggesting an interaction with internal routes. Microbiota metabolites derived from these phenolics were also taken into account; thereby, homovanillic alcohol and tyrosol were identified and quantified in urine samples after enzymatic de-conjugation, concluding the metabolic profile of HT.

Conclusions

Our results suggest that different dosages of HT, HTA, and DOPAC do not provide a linear, dose-dependent plasma concentration or excretion in urine, both of which can be affected by the saturation of first-phase metabolic processes and intestinal transporters.

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Acknowledgments

The authors are grateful to the Intramural Project (Ref. 201170E041). We thank the English expert reviewer (Dr. David James Walker) for the revision of the English style and grammar.

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Authors and Affiliations

  1. Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Espinardo, Murcia, Spain

    Raúl Domínguez-Perles, Federico Ferreres & Angel Gil-Izquierdo

  2. Department of Research and Development, Seprox BIOTECH S.L., Madrid, Spain

    David Auñón

Authors
  1. Raúl Domínguez-Perles
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  2. David Auñón
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  3. Federico Ferreres
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  4. Angel Gil-Izquierdo
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Correspondence to Angel Gil-Izquierdo.

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Domínguez-Perles, R., Auñón, D., Ferreres, F. et al. Gender differences in plasma and urine metabolites from Sprague–Dawley rats after oral administration of normal and high doses of hydroxytyrosol, hydroxytyrosol acetate, and DOPAC. Eur J Nutr 56, 215–224 (2017). https://doi.org/10.1007/s00394-015-1071-2

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  • DOI: https://doi.org/10.1007/s00394-015-1071-2

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