Simultaneous determination of phenolic compounds in table olives and plasma by LC-MS/MS. Pharmacokinetic parameters in rats and humans after the consumption of Arbequina variety.
[eng] Table olives are an important source of phenolic compounds, whose beneficial health effects have been widely demonstrated. Therefore, the present thesis aims to assess the different phenolic compounds in Arbequina table olives and their determination in plasma of rats and healthy human volunte...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/185399 |
| Acceso en línea: | https://hdl.handle.net/2445/185399 http://hdl.handle.net/10803/674175 |
| Access Level: | acceso abierto |
| Palabra clave: | Farmacocinètica Olives Polifenols Plasma sanguini Cromatografia de líquids Espectrometria de masses Pharmacokinetics Olive Polyphenols Blood plasma Liquid chromatography Mass spectrometry |
| Sumario: | [eng] Table olives are an important source of phenolic compounds, whose beneficial health effects have been widely demonstrated. Therefore, the present thesis aims to assess the different phenolic compounds in Arbequina table olives and their determination in plasma of rats and healthy human volunteers after the consumption of this food. Firstly, the composition of Arbequina table olives was analysed by LC-ESI-MS/MS. In total, 16 phenolic compounds were determined (1.0 g/kg), being hydroxytyrosol, luteolin and verbascoside the most abundant ones (∼90%). Subsequently, a new method based on liquid-liquid extraction followed by LC-ESI-MS/MS analysis was developed. Since the validation gave suitable results for linearity, sensibility, accuracy, precision and recoveries, the method could be applied for pre-clinical studies. Hence, Sprague-Dawley rats were orally administered with table olives at 3.85 and 7.70 g/kg. Out of 16 polyphenols found in table olives, only 7 compounds were determined in rat plasma (p-coumaric acid, hydroxytyrosol, luteolin, luteolin-7-O-glucoside, salidroside, tyrosol, and verbascoside) from whose concentrations pharmacokinetic parameters were evaluated. Results indicated relatively fast absorption from 30 min up to 1 h for all the compounds. At both doses the highest AUC was achieved by p- coumaric acid, followed by hydroxytyrosol, and salidroside. Hydroxytyrosol underwent extensive metabolism, being two sulfates the most abundant (∼86%), followed by hydroxytyrosol (∼10%) and two glucuronides (∼4%). Half-life was ranging from 1 h for salidroside up to 5 hours for tyrosol. Then, the first part of clinical trial was performed with human volunteers that received 60 and 120 olives. The method validated in human plasma with satisfactory results allowed the determination of 6 compounds (vanillic acid, hydroxytyrosol, salidroside, luteolin, verbascoside, and hydroxytyrosol acetate) and subsequently the pharmacokinetics was evaluated. Tmax was ranging from 30 min up to 90 min. The highest AUC was reached by vanillic acid, followed by hydroxytyrosol acetate, and hydroxytyrosol. Hydroxytyrosol had similar extensive metabolism as in rats, when two sulfates were the most abundant (∼85%), followed by hydroxytyrosol (∼10%) and two glucuronides (∼5%). Half-life was ranging from 4 h for luteolin, salidroside and hydroxytyrosol acetate up to 7 hours for hydroxytyrosol and verbascoside. Finally, the second part of clinical trial when human volunteers daily ingested 60 olives for 30 days was performed. In total, 9 phenolic compounds were determined. No significant differences were observed within the plasmatic concentrations of vanillic acid, catechol, quercetin, salidroside, apigenin, whereas the plasmatic concentrations of p-coumaric acid, hydroxytyrosol (together with two sulfates), luteolin, and hydroxytyrosol acetate increased over time with repeated intake of Arbequina table olives. In conclusion, the present thesis expanded the knowledge about the pharmacokinetics of phenolic compounds contained in Arbequina table olives in rats and humans after their oral administration that might provide a basis for the future use of table olives as a functional food. |
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