Compounds In Olive Oil Research Articles

Determination of volatile compounds responsible for sensory characteristics from Brazilian extra virgin olive oil using HS-SPME/GC-MS direct method.

Producing of extra virgin olive oils (EVOOs) containing pleasant sensory notes depends on fruits quality and production process and is strongly associated with their classification that is based on aroma and sensory taste. Consolidated as an efficient method, the direct headspace solid phase microextraction technique (HS-SPME) was utilized to characterize the volatile organic compounds (VOCs) profile, which contributes to the aroma of olive oils from southwestern (Serra da Mantiqueira region) and southern (Campanha Gaúcha region) Brazil. In this work, the relationship between the VOCs and sensory characteristics has been established; 19 EVOO samples (12 from Campanha Gaúcha and 7 from Serra da Mantiqueira) were studied. Indeed, the main volatile compounds were analyzed and grouped by their classification as well stood up with the trained sensorial panel perceptions. Relevant correlation between artichoke notes and ripe EVOO and between herbaceous notes and green EVOO was found. Additional correlations were observed for C5 and C6 VOCs with green and fruit/floral notes. The results denote the high quality among the samples and imply that besides the genetic factor, ripe or green classification influenced the volatile composition. PRACTICAL APPLICATION: As the Brazilian olive oil production is increasing, knowing about different sensory characteristics and its correlation with the volatile compounds of extra virgin olive oil represents a good tool to improve the quality. Moreover, the application of direct SPME method was possible evidence in the differentiation of ripe and green olive oils, beyond the production region and in consonance with its sensory notes and characteristics.

Antioxidant quantification in different portions obtained during olive oil extraction process in an olive oil press mill.

Different antioxidant compounds are generally transferred from olives to olive oil during the production process. This work characterized the principal total bioactive compounds (tocopherols and phenols) in olives, olive oil and by-products of four cultivars grown in Calabrian areas (southern Italy), considering the effect of harvesting period. Antioxidant capacity, total and individual phenolic compounds were also analysed. Drupes, olive paste, pomace and olive wastewater showed similar phenolic compounds, while olive oil possessed a different composition, suggesting that phenols are not only transferred from drupe to oil, but also they change during oil production. Tocopherols varied among cultivars and harvesting period: generally, they were more abundant in samples produced in the first harvesting period. Qualitative and quantitative differences in phenolic composition and antioxidant activity were significantly found among cultivars in all the matrices. The highest amount of total phenolic antioxidants ended up in olive wastewater with variability due to the olive cultivar, while only a small part of them finished in the oil. This work shows evidence that the availability of bioactive compounds in different portions from the olive oil extraction belong to different varietal origins. In particular, new information was acquired on Ottobratica Calipa, a new olive clone, that produced an olive oil with an interesting antioxidant amount. © 2020 Society of Chemical Industry.

Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases.

The growing incidence of cardiovascular disease (CVD) has promoted investigations of natural molecules that could prevent and treat CVD. Among these, hydroxytyrosol, a polyphenolic compound of olive oil, is well known for its antioxidant, anti-inflammatory, and anti-atherogenic effects. Its strong antioxidant properties are due to the scavenging of radicals and the stimulation of synthesis and activity of antioxidant enzymes (SOD, CAT, HO-1, NOS, COX-2, GSH), which also limit the lipid peroxidation of low-density lipoprotein (LDL) cholesterol, a hallmark of atherosclerosis. Lowered inflammation and oxidative stress and an improved lipid profile were also demonstrated in healthy subjects as well as in metabolic syndrome patients after hydroxytyrosol (HT) supplementation. These results might open a new therapeutic scenario through personalized supplementation of HT in CVDs. This review is the first attempt to collect together scientific literature on HT in both in vitro and in vivo models, as well as in human clinical studies, describing its potential biological effects for cardiovascular health.

Concentration of Potentially Bioactive Compounds in Italian Extra Virgin Olive Oils from Various Sources by Using LC-MS and Multivariate Data Analysis.

High quality extra virgin olive oils represent an optimal source of nutraceuticals. The European Union (EU) is the world’s leading olive oil producer, with the Mediterranean region as the main contributor. This makes the EU the greatest exporter and consumer of olive oil in the world. However, small olive oil producers also contribute to olive oil production. Beneficial effects on human health of extra virgin olive oil are well known, and these can be correlated to the presence of vitamin E and phenols. Together with the origin of the olives, extraction technology can influence the chemical composition of extra virgin olive oil. The aim of this study was to investigate the concentration of potentially bioactive compounds in Italian extra virgin olive oils from various sources. For this purpose, vitamin E and phenolic fractions were characterized using high-performance liquid chromatography (HPLC) coupled with fluorescence, photodiode array and mass spectrometry detection in fifty samples of oil pressed at industrial plants and sixty-six samples of oil produced in low-scale mills. Multivariate statistical data analysis was used to determine the applicability of selected phenolic compounds as potential quality indicators of extra virgin olive oils.

Study of the influence of technological coadjuvants on enzyme activities and phenolic and volatile compounds in virgin olive oil by a response surface methodology approach

Although the use of technological coadjuvants during virgin olive oil extraction helps in maximising the process efficiency, it could influence the characteristics of the final product. So far, why this happens is still not understood. In this context, an influence on the biochemical activities occurring during the malaxation step was supposed, and this hypothesis was verified by a response surface methodology approach. The effect of two independent variables, namely malaxation temperature and amount of coadjuvant, on polyphenol oxidase, peroxidase and lipoxygenase activities as well as on the corresponding phenolic and volatile compounds of the oils was studied. Calcium carbonate enhanced the activities of oxidases leading to a reduction of phenolic compounds, which were negatively correlated with the coadjuvant usage. Micronized natural talc behaved the opposite but had a general weaker influence, often overcome by that of mixing temperature. A significant shift of the olive paste pH toward that optimal for oxidases enzymes was highlighted under the use of calcium carbonate. The findings evidenced a “side effect” of the use of technological coadjuvants in the context of virgin olive oil extraction.

Chemical Profile and Antibacterial Activity of a Novel Spanish Propolis with New Polyphenols also Found in Olive Oil and High Amounts of Flavonoids.

Propolis is a natural product obtained from hives. Its chemical composition varies depending on the flora of its surroundings, but nevertheless, common for all types of propolis, they all exhibit remarkable biological activities. The aim of this study was to investigate the chemical composition and antimicrobial activity of a novel Spanish Ethanolic Extract of Propolis (SEEP). It was found that this new SEEP contains high amounts of polyphenols (205 ± 34 mg GAE/g), with unusually more than half of this of the flavonoid class (127 ± 19 mg QE/g). Moreover, a detailed analysis of its chemical composition revealed the presence of olive oil compounds (Vanillic acid, 1-Acetoxypinoresinol, p-HPEA-EA and 3,4-DHPEA-EDA) never detected before in propolis samples. Additionally, relatively high amounts of ferulic acid and quercetin were distinguished, both known for their important therapeutic benefits. Regarding the antimicrobial properties of SEEP, the minimal inhibitory and bactericidal concentrations (MIC and MBC) against Staphylococcus epidermidis strains were found at the concentrations of 240 and 480 µg/mL, respectively. Importantly, subinhibitory concentrations were also found to significantly decrease bacterial growth. Therefore, the results presented here uncover a new type of propolis rich in flavonoids with promising potential uses in different areas of human health.

Oleuropein promotes hippocampal LTP via intracellular calcium mobilization and Ca2+-permeable AMPA receptor surface recruitment

Oleuropein (OLE), a major phenolic compound in olive oil, has been demonstrated to possess several pharmacological properties, including neuroprotection. However, the cognitive effects of OLE and its action mechanism have remained unclear. Here, we examined the effect of OLE on long-term potentiation (LTP) using field excitatory postsynaptic potential recorded in the CA1 region of both wild-type and 5XFAD mouse hippocampal slice preparations. In initial experiments with wild-type mice, 100 μM/1 h of OLE produced significant enhancements in the LTPs of Schaffer collateral synapses in the CA1 regions of treated mice, as compared to the vehicle-treated controls. As assessed by surface biotinylation and Western blot analysis, OLE caused a significant increase in protein kinase A (PKA)-mediated phosphorylation and the surface expression of GluA1 containing calcium permeable- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) in the hippocampus. Furthermore, we found that OLE enhanced LTP induction, while GluA1 phosphorylation occurred in an N-methyl-d-aspartate receptors (NMDARs)-independent manner. The OLE-induced CP-AMPAR trafficking resulted from elevated intracellular Ca2+ levels via regulation of phospholipase C (PLC). Consistently, we also found involvement of NMDAR-independent LTP and GluA1 phosphorylation in 5XFAD transgenic mice hippocampal slices treated with OLE. Together, our findings indicate that OLE may regulate beneficial effects on memory through the facilitation of CP-AMPAR trafficking and synaptic transmission.

Correlation structure between agroclimatic big data and EVOO fatty acid profile determined by GC and NMR spectra

AbstractFatty acids are the major compounds in olive oils, and the determination of their profile is very useful in order for the authentication of the high quality of extra virgin olive oil (EVOO) and the evaluation of its purity and traceability. This work considers the estimations of saturated (SAFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids obtained by gas chromatography (GC), 13C (carbonyl, C‐16, and aliphatic carbons regions), and 1H NMR spectra. The aim of this paper is to analyze the correlation structure being between the abovementioned fatty acids estimations and some long‐run agroclimatic measurements (temperature, humidity, wind speed and direction, radiation, precipitation, and evapotranspiration), which were downloaded from the official website of the Andalusian Automatic Weather Stations (AWSs). The versatile graphical possibilities of the free software R‐project allow the design of computational programs providing interesting conclusions about the described correlations as a function of month, variety of olive, and protected designation of origin (PDO). The statistically significant correlations could determine relevant agroclimatic information to be included, in a further research, among the explanatory variables in regression models in order to improve the estimation of fatty acid profile of EVOOs, considered as a quality parameter in their authentication.

Utilisation of the OliveNet™ Library to investigate phenolic compounds using molecular modelling studies in the context of Alzheimer’s disease

Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that affects over 47 million people worldwide, and is the most common form of dementia. There is a vast body of literature demonstrating that the disease is caused by an accumulation of toxic extracellular amyloid-β (Aβ) peptides and intracellular neurofibrillary tangles that consist of hyperphosphorylated tau. Adherence to the Mediterranean diet has been shown to reduce the incidence of AD and the phenolic compounds in extra virgin olive oil, including oleocanthal, have gained a significant amount of attention. A large number of these ligands have been described in the pre-existing literature and 222 of these compounds have been characterised in the OliveNet™ database. In this study, molecular docking was used to screen the 222 phenolic compounds from the OliveNet™ database and assess their ability to bind to various forms of the Aβ and tau proteins. The phenolic ligands were found to be binding strongly to the hairpin-turn of the Aβ1−40 and Aβ1−42 monomers, and binding sites were also identified in the tau fibril protein structures. Luteolin-4′-O-rutinoside, oleuricine A, isorhoifolin, luteolin-7-O-rutinoside, cyanidin-3-O-rutinoside and luteolin-7,4-O-diglucoside were predicted to be novel lead compounds. Molecular dynamics (MD) simulations performed using well-known olive ligands bound to Aβ1−42 oligomers highlighted that future work may examine potential anti-aggregating properties of novel compounds in the OliveNet™ database. This may lead to the development and evaluation of new compounds that may have efficacy against Alzheimer’s disease.

Phenolic compounds and fatty acids content of some West Algerian olive oils

Olive represents the most widespread fruit cultivated in Algeria. Olive oil is the primary source of added fat in the Mediterranean diet with health benefits of which have been verified for millennia. Interest in phenolic compounds in olive oil has increased due to its antioxidant activity, which plays a very important role in human health. The present study is carried out to study the phenolic compounds and fatty acids profile of some olive oils from western Algeria. The quality parameters (acidity, peroxide value, K232, K270), tocopherol analysis, fatty acid composition and phenolic profile were determined by High performance chromatography (HPLC). The results showed that chemlal oil (SBA) recorded the highest level of tocopherol-α with 228.12 mg/Kg. Regarding the fatty acid composition, oleic acid was the most dominant, oil Oleaster (Bensekrane) records the highest percentage (72.80%) of oleic acid. The quantitative data on the phenolic content of the seven samples revealed that chemlal oil (SBA) had the highest level of polyphenols (328.99 mg/Kg). However, Sigoise oil (Sebra1) was characterized by the highest levels of tyrosol and hydroxytyrosol (15.89 mg/kg and 22.42 mg/kg, respectively). The highest concentrations of oleuropein derivatives and ligstroside derivatives were observed in chemlal oil (SBA) and the recoreded values were 105.97 mg/Kg and 83.49 mg/Kg, respectively. Chemlal oil (SBA) was characterized by the highest amount of lignans (35.93 mg/Kg), luteolin (10.16 mg/Kg) and apigenin (5.44 mg/Kg). Oleocanthal was found in all the tested samples and it was higher in Chemlal oil (102.43 mg/kg).

Varietal Effect on the Concentration and Anti-Inflammatory Activity of Hydroxytyrosol in French Olive Oils.

Numerous studies have been carried out on the bioactive properties of hydroxytyrosol (HT) in olive oils (OOs), although there are few reports comparing anti-inflammatory activity among different olive varieties or regions of production. The purpose of this study was to investigate the in vitro inflammatory action of HT in extracts of four OO varieties in the Languedoc region of the French Mediterranean. Factors other than cultivar were eliminated, which enabled unambiguous varietal differences to be identified. Purified extracts of OO were obtained using an optimized solid-phase extraction procedure by which only polar compounds were recovered. High performance liquid chromatography-photodiode array detection-tandem mass spectrometry was used to identify and quantify HT and oleacein in the extracts. The total polyphenol concentration ranged from 93.00 mg gallic acid equivalent/kg OO for Picholine to 27 mg gallic acid equivalent for Verdale OOs. The concentrations of HT in Picholine, Olivère, and Lucques varieties were 25.3, 18.8 and 12.1 mg/kg, respectively, whereas the concentration of HT in Verdale OOs was less, 1 mg/kg. The in vitro anti-inflammatory response of purified OO extracts, evaluated by the inhibition of nitric oxide release in lipopolysaccharide-induced interferon-γ activated J774.A1 macrophages, strongly correlated with total polyphenol content (R2 > 0.995). The effect increased asymptotically between the equivalent of 2 and 37 mg of OO, reaching, at the maximum tested concentration, 90%, 75%, 62%, and 30% activity for Picholine, Olivière, Lucques, and Verdale, respectively. The results presented here clearly show that, by comparison with authentic standards, the activity of HT in OO extracts was enhanced in a concentration-dependent manner, varying from 3-fold at the highest extract concentration to over 6.5-fold at the lowest extract concentration. Therefore, the anti-inflammatory activity of OOs should be rationalized on the basis of whole extracts rather than solely on the concentration of HT or other bioactive compounds in OO.

Exploring the Scientific Interest for Olive Oil Origin: A Bibliometric Study from 1991 to 2018

The authenticity and traceability of olive oils have been a growing concern over the past decades, generating numerous scientific studies. This article applies the tools of bibliometric analyses to explore the evolution and strategic orientation of the research focused on olive oil geographical and varietal origins. A corpus of 732 papers published in 178 different journals between 1991 and 2018 was considered. The most productive journals, authors and countries are highlighted, as well as the most cited articles associated with specific analytical techniques. A cluster analysis on the keywords generates 8 main themes of research, each focused on different analytical techniques or compounds of interest. A network between these thematic clusters and the main authors indicates their area of expertise. The metabolomics methods are drawing increasing interest and studies focused on the relationships between the origin and the sensory or nutritional properties provided by minor compounds of olive oils appear to be future lines of research.

Is Extra Virgin Olive Oil an Ally for Women's and Men's Cardiovascular Health?

Noncommunicable diseases are long-lasting and slowly progressive and are the leading causes of death and disability. They include cardiovascular diseases (CVD) and diabetes mellitus (DM) that are rising worldwide, with CVD being the leading cause of death in developed countries. Thus, there is a need to find new preventive and therapeutic approaches. Polyphenols seem to have cardioprotective properties; among them, polyphenols and/or minor polar compounds of extra virgin olive oil (EVOO) are attracting special interest. In consideration of numerous sex differences present in CVD and DM, in this narrative review, we applied “gender glasses.” Globally, it emerges that olive oil and its derivatives exert some anti-inflammatory and antioxidant effects, modulate glucose metabolism, and ameliorate endothelial dysfunction. However, as in prescription drugs, also in this case there is an important gender bias because the majority of the preclinical studies are performed on male animals, and the sex of donors of cells is not often known; thus a sex/gender bias characterizes preclinical research. There are numerous clinical studies that seem to suggest the benefits of EVOO and its derivatives in CVD; however, these studies have numerous limitations, presenting also a considerable heterogeneity across the interventions. Among limitations, one of the most relevant in the era of personalized medicine, is the non-attention versus women that are few and, also when they are enrolled, sex analysis is lacking. Therefore, in our opinion, it is time to perform more long, extensive and lessheterogeneous trials enrolling both women and men.

Characterization of the Key Odorants in High-Quality Extra Virgin Olive Oils and Certified Off-Flavor Oils to Elucidate Aroma Compounds Causing a Rancid Off-Flavor

To identify the odorants responsible for a rancid off-flavor in olive oils, first, the key aroma compounds in a premium extra virgin olive oil (PreOO1) were characterized by the sensomics approach and were then compared to those present in a certified rancid off-flavor olive oil (RanOO1) obtained from the International Olive Council (IOC). By application of an aroma extract dilution analysis, 46 odorants were detected and subsequently identified in PreOO1 and 35 odorants in RanOO1, respectively. After quantitation by stable isotope dilution assays, calculation of odor activity values (OAVs; ratio of concentration to odor threshold) revealed only 5 odorants with OAVs > 10 in PreOO1, while 13 odorants showed OAVs > 100 in RanOO1, with (E,Z)-2,4-decadienal, hexanoic acid, octanal, hexanal, (E)-2-octenal, and (Z)-2-nonenal being among the most odor-active compounds. Thus, marker aroma compounds for this off-flavor type could be suggested. Additionally, based on the OAVs obtained, the overall aroma profiles of both oils were mimicked by aroma recombination experiments. As proof of concept, 16 marker odorants were quantitated in two additional extra virgin olive oils and in eight further olive oils eliciting a rancid off-flavor. Application of a principal component analysis (PCA) and a hierarchical cluster analysis successfully discriminated both categories of olive oils. In the 12 olive oils used, acetic acid showed the highest Pearson coefficient between the perceived intensity of the rancid defect and the odorant concentration. In particular, (E,Z)- and (E,E)-2,4-decadienal and (Z)-2-nonenal can be suggested as chemical markers for olive oil rancidity in combination with positive aroma markers, for example, acetaldehyde and (Z)-3-hexenal.

Crosstalk between hydroxytyrosol, a major olive oil phenol, and HIF-1 in MCF-7 breast cancer cells

Olive oil intake has been linked with a lower incidence of breast cancer. Hypoxic microenvironment in solid tumors, such as breast cancer, is known to play a crucial role in cancer progression and in the failure of anticancer treatments. HIF-1 is the foremost effector in hypoxic response, and given that hydroxytyrosol (HT) is one of the main bioactive compounds in olive oil, in this study we deepen into its modulatory role on HIF-1. Our results in MCF-7 breast cancer cells demonstrate that HT decreases HIF-1α protein, probably by downregulating oxidative stress and by inhibiting the PI3K/Akt/mTOR pathway. Strikingly, the expression of HIF-1 target genes does not show a parallel decrease. Particularly, adrenomedullin and vascular endothelial growth factor are up-regulated by high concentrations of HT even in HIF-1α silenced cells, pointing to HIF-1-independent mechanisms of regulation. In fact, we show, by in silico modelling and transcriptional analysis, that high doses of HT may act as an agonist of the aryl hydrocarbon receptor favoring the induction of these angiogenic genes. In conclusion, we suggest that the effect of HT in a hypoxic environment is largely affected by its concentration and involves both HIF-1 dependent and independent mechanisms.

Application of deep eutectic solvents for the extraction of phenolic compounds from extra-virgin olive oil.

A HPLC-DAD/ESI-MS method has been developed and validated for the analysis of the most representative phenolic compounds in extra-virgin olive oil (EVOO) samples using a green extraction approach based on deep eutectic solvents (DESs) at room temperature. We examined ten DESs based on choline chloride and betaine in combination with different hydrogen bond donors comprising six alcohols, two organic acids, and one urea. Five phenolic compounds, belonging to the classes of secoiridoids and phenolic alcohols, were selected for the evaluation of extraction efficiency. A betaine-based DES with glycerol (molar ratio 1:2) was found to be the most effective for extracting phenolic compounds as compared to a conventional solvent. The optimization of the extraction method involved the study of the quantity of water to be added to the DES and evaluation of the sample-to-solvent ratio optimal condition. Thirty percent of water added to DES and sample to solvent ratio 1:1 (w/v) were selected as the best conditions. The chromatographic method was validated by studying LOD, LOQ, intraday and interday retention time precision, and linearity range. Recovery values obtained spiking seed oil sample aliquots with standard compounds at 5 and 100μg/g concentration were in the range between 75.2% and 98.7%.

Effect of the Refining Process on Total Hydroxytyrosol, Tyrosol, and Tocopherol Contents of Olive Oil.

The impact of the olive oil refining process on major antioxidant compound levels was evaluated by means of UHPLC analysis of lampante olive oils collected at different stages of the refining procedure (degumming, chemical and physical flash neutralization, bleaching, and deodorization). For this purpose, the evolution of the tocopherol fraction was investigated by means of the UHPLC-FL method, while the influence of the refining process on the total hydrolyzed phenolic content was assessed by measuring hydroxytyrosol and tyrosol levels after acid hydrolysis of the phenolic extracts. Refining was found to have a marked effect on total hydroxytyrosol and tyrosol contents, as they are completely removed in the early steps of the refining procedure. In contrast, the variation trends of tocopherols are not always clear-cut, and significant decreases in content from 7% to 16% were only revealed during refining in four out of nine samples. In addition, five of the nine refined oils showed final tocopherol concentrations higher than 200 mg/kg, the limit imposed by international standards regarding the content of such compounds in commercial olive oils. This study supports the need for a revision of the International Olive Oil Council (IOC) standard relative to the limit established for tocopherol addition to refined oils to avoid possible legal and economic trade issues.

Deep eutectic solvents (DES) as green extraction media for antioxidants electrochemical quantification in extra-virgin olive oils

A new electroanalytical method has been developed for the determination of polar antioxidant compounds in extra virgin olive oils. This method is based on the extraction of polar antioxidant compounds from extra-virgin olive oils by means of a deep eutectic solvent and their determination by a modified screen-printed electrode platform. The platform sensitivity was increased by modifying the working electrode with MWCNT and TiO2 nanoparticles as modifiers and Nafion as a binder. The platform showed very good sensitivity in detecting polar antioxidant compounds in extra-virgin olive oils in a fairly wide range of concentrations. The measurements were performed by using square wave voltammetry. The extraction was performed without using organic solvents, making the method environmentally friendly. The proposed method has been compared with a common spectrophotometric one, the results appeared in good agreement. The method is sufficiently easy and quick to be used for screening analyses of polar antioxidant compounds in extra-virgin olive oils on the field.

Diet and cancer: Investigating the mechanisms of polyphenolic compounds in extra virgin olive oil

Diet and cancer: Investigating the mechanisms of polyphenolic compounds in extra virgin olive oil

Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats.

Oleocanthal (OLC), a phenolic compound of extra virgin olive oil (EVOO), has emerged as a potential therapeutic agent against a variety of diseases due to its anti-inflammatory activity. The aim of the present study is to explore its in vivo intestinal absorption and metabolism. An in situ perfusion technique in rats was used, involving simultaneous sampling from the luminal perfusate and mesenteric blood. Samples were analysed by UHPLC–MS–MS for the presence of oleocanthal (OLC) and its metabolites. OLC was mostly metabolized by phase I metabolism, undergoing hydration, hydrogenation and hydroxylation. Phase II reactions (glucuronidation of hydrogenated OLC and hydrated metabolites) were observed in plasma samples. OLC was poorly absorbed in the intestine, as indicated by the low effective permeability coefficient (2.23 ± 3.16 × 10−5 cm/s) and apparent permeability coefficient (4.12 ± 2.33 × 10−6 cm/s) obtained relative to the values of the highly permeable reference compound levofloxacin (LEV). The extent of OLC absorption reflected by the area under the mesenteric blood-time curve normalized by the inlet concentration (AUC) was also lower than that of LEV (0.25 ± 0.04 vs. 0.64 ± 0.03, respectively). These results, together with the observed intestinal metabolism, suggest that OLC has a moderate-to-low oral absorption; but higher levels of OLC are expected to reach human plasma vs. rat plasma.