Tissue Distribution of Oleocanthal and Its Metabolites after Oral Ingestion in Rats

Abstract

Claims for the potential health benefits of oleocanthal (OLC), a dietary phenolic compound found in olive oil, are based mainly on in vitro studies. Little is known about the tissue availability of OLC, which is rapidly metabolized after ingestion. In this study, the distribution of OLC and its metabolites in rat plasma and tissues (stomach, intestine, liver, kidney, spleen, lungs, heart, brain, thyroid and skin) at 1, 2 and 4.5 h after the acute intake of a refined olive oil containing 0.3 mg/mL of OLC was examined by LC-ESI-LTQ-Orbitrap-MS. OLC was only detected in the stomach and intestine samples. Moreover, at 2 and 4.5 h, the concentration in the stomach decreased by 36% and 74%, respectively, and in the intestine by 16% and 33%, respectively. Ten OLC metabolites arising from phase I and phase II reactions were identified. The metabolites were widely distributed in rat tissues, and the most important metabolizing organs were the small intestine and liver. The two main circulating metabolites were the conjugates OLC + OH + CH3 and OLC + H2O + glucuronic acid, which may significantly contribute to the beneficial health effects associated with the regular consumption of extra virgin olive oil. However, more studies are necessary to determine the concentrations and molecular structures of OLC metabolites in human plasma and tissues when consumed with the presence of other phenolic compunds present in EVOO.

Oleacein Intestinal Permeation and Metabolism in Rats Using an In Situ Perfusion Technique

“…Accurate masses and the isotopic pattern (through the Formula Finder feature in Xcalibur 3.0 software (ThermoFisher Scientific, Hemel Hempstead, UK) were used to select the elemental composition of each OLEA derivative. In addition, metabolites were confirmed by comparison with those reported in the literature [21,22] and with a similar compound [6,36,37]. MS n measurements were performed to obtain information about fragment ions generated in the linear ion trap within the same analysis.…”

Metabolomics Technologies for the Identification and Quantification of Dietary Phenolic Compound Metabolites: An Overview

“…The advantages are the high trapping capacity and MS n scanning function of the LTQ along with accurate mass measurements, resulting in greater throughput and identification of major or trace metabolites. To date, the LTQ-Orbitrap mass analyzer is the most popular platform used in dietary PC metabolomics research, applied to study the metabolism of compounds such as (-)-epicatechin [87], oleocanthal [93,94], oleacein [95], daidzein [88], hesperetin, and hesperidin [92], and to identify PCM in biological samples after the intake of foods or beverages [41,64,66,81,84]. As can be seen in Table 2, negative ESI is the most routinely used mode in PCM analysis.…”

“…Table 3 summarizes the main chromatographic and MS conditions employed in targeted studies of PCM in urine and plasma samples. It is well-known that due to the lack of bioanalytical standards for some PCM, various strategies have been used trying to solve this problem: (i) quantification of PCM using the calibration curves corresponding to their phenolic precursors or with the most structurally similar compound [42,43], (ii) expressing the concentration as equivalents of parent compounds [71,94], (iii) expressing the concentration as ratios [29,93,95,115], and (iv) the synthesis of the target metabolites [39]. In the case of the expression of the concentration as ratios, the peak abundance ratio (analyte/internal standard) and the concentration ratio (analyte/internal standard) are used [115].…”

LC-ESI-LTQ-Orbitrap-MS for Profiling the Distribution of Oleacein and Its Metabolites in Rat Tissues

“…To avoid compound oxidation, the samples were handled in a room with filtered light and kept on ice throughout. The clean-up of the biological matrix (protein precipitation) was performed using a previously developed method [21].…”

“…In addition, the stability of OLEA under low pH conditions and permeability in Caco-2 cells, and in isolated rat intestine has been studied [18] as well as its fecal microbial metabolism in vivo [19]. The distribution and accumulation of EVOO polyphenols [20] and oleocanthal [21] has also been determined in rat tissues. The health-enhancing properties of OLEA cannot be fully understood without further analysis of its absorption, tissue distribution, metabolism, and excretion.…”