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

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, hydr...

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Bibliographic Details
Published in:European journal of nutrition 2017-02, Vol.56 (1), p.215-224
Main Authors: Domínguez-Perles, Raúl, Auñón, David, Ferreres, Federico, Gil-Izquierdo, Angel
Format: Article
Language:English
Subjects:
3,4-Dihydroxyphenylacetic Acid - administration & dosage
3,4-Dihydroxyphenylacetic Acid - blood
3,4-Dihydroxyphenylacetic Acid - pharmacokinetics
3,4-Dihydroxyphenylacetic Acid - urine
Administration, Oral
Animals
Biological Availability
Chemistry
Chemistry and Materials Science
Dose-Response Relationship, Drug
Female
Homovanillic Acid - urine
Male
Nutrition
Olive Oil - administration & dosage
Original Contribution
Phenols - administration & dosage
Phenols - blood
Phenols - pharmacokinetics
Phenols - urine
Phenylethyl Alcohol - administration & dosage
Phenylethyl Alcohol - analogs & derivatives
Phenylethyl Alcohol - blood
Phenylethyl Alcohol - pharmacokinetics
Phenylethyl Alcohol - urine
Rats
Rats, Sprague-Dawley
Sex Factors
Tandem Mass Spectrometry
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Summary: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.
ISSN:1436-6207
1436-6215
1435-1293
DOI:10.1007/s00394-015-1071-2