Identification of novel F2-isoprostane metabolites by specific UDP-glucuronosyltransferases.

UDP-glucuronosyltransferases (UGTs) catalyze the conjugation of glucuronic acid with endogenous and exogenous lipophilic small molecules to facilitate their inactivation and excretion from the body. This represents approximately 35 % of all phase II metabolic transformations. Fatty acids and their oxidized eicosanoid derivatives can be metabolized by UGTs. F2-isoprostanes (F2-IsoPs) are eicosanoids formed from the free radical oxidation of arachidonic acid. These molecules are potent vasoconstrictors and are widely used as biomarkers of endogenous oxidative damage. An increasing body of evidence demonstrates the efficacy of measuring the ß-oxidation metabolites of F2-IsoPs rather than the unmetabolized F2-IsoPs to quantify oxidative damage in certain settings. Yet, the metabolism of F2-IsoPs is incompletely understood. This study sought to identify and characterize novel phase II metabolites of 15-F2t-IsoP and 5-epi-5-F2t-IsoP, two abundantly produced F2-IsoPs, in human liver microsomes (HLM). Utilizing liquid chromatography-mass spectrometry, we demonstrated that glucuronide conjugates are the major metabolites of these F2-IsoPs in HLM. Further, we showed that these molecules are metabolized by specific UGT isoforms. 15-F2t-IsoP is metabolized by UGT1A3, 1A9, and 2B7, while 5-epi-5-F2t-IsoP is metabolized by UGT1A7, 1A9, and 2B7. We identified, for the first time, the formation of intact glucuronide F2-IsoPs in human urine and showed that F2-IsoP glucuronidation is reduced in people supplemented with eicosapentaenoic and docosahexaenoic acids for 12 weeks. These studies demonstrate that endogenous F2-IsoP levels can be modified by factors other than redox mechanisms.

Phytoprostanes and phytofurans: Bioactive compounds in aerial parts of Acacia cyanophylla Lindl.

The relevance of oxylipins as biomarkers of oxidative stress has been established in recent years. Phytoprostanes and phytofurans are plant metabolites derived from peroxidation of α-linolenic acid (ALA) induced by ROS. Previous findings have suggested new valuable biological properties for these new active compounds in the frame of diverse pathophysiological situations and health constraints. Lipidomic profiling of different aerial parts of the same Acacia cyanophylla Lindl. specimen, was evaluated for the first time here, using LC-MS/MS technology. Analysis revealed the existence of six PhytoPs and three PhytoFs. Stems have the highest amount of these metabolites with 179.35 ng/g and 320.79 ng/g respectively. This first complete profile paves the way to explore Acacia cyanophylla Lindl. as a source of plant oxylipins for therapeutic or pharmaceutical uses.

Omega-3 to omega-6 fatty acid oxidation ratio as a novel inflammation resolution marker for metabolic complications in obesity.

BACKGROUND AND AIMS: The oxidative metabolism of polyunsaturated fatty acids (PUFAs) leads to bioactive isoprostanoids. The aim was to establish the associations of a complete urinary isoprostanoid profiling in a cohort study of carefully phenotyped obese subjects to determine possible potential differential implications for omega-6 PUFA- and omega-3 PUFA-derived isoprostanoids for obesity, metabolic indicators, and inflammation. METHODS AND RESULTS: PUFA peroxidation compounds were determined in urine samples from obese human subjects (n = 46) by liquid chromatography coupled to tandem mass spectrometry. Increased omega-6 arachidonic acid (AA) oxidation, mainly represented by 5-F2c isoprostane (5-F2c-IsoP) and metabolites of 15-F2t-IsoP, was associated with body mass index, glycated hemoglobin (HbA1c) and mean arterial blood pressure. In addition, we identified the omega-3 PUFA-derived urinary metabolites 14-F4t-NeuroP from docosahexaenoic acid (DHA) and 5-F3t-IsoP from eicosapentaenoic acid (EPA), which declined with age. The omega-3 to omega-6 oxidation ratio was a significant predictor of inflammation in obesity. CONCLUSION: The findings point to full urinary isoprostanoid profiling as a more sensitive measure of PUFA oxidative stress in obesity-induced metabolic complications compared with individual isoprostanoid measures. Furthermore, the results suggest the balance between the omega-3 and omega-6 PUFA oxidation as determinative for the consequences of oxidative stress on inflammation in obesity.

Salivary lipid mediators: Key indexes of inflammation regulation in heart failure disease.

Cardiovascular diseases (CVDs) are the leading cause of premature death and disability in humans and their incidence continues to increase. Oxidative stress and inflammation have been recognized as key pathophysiological factors in cardiovascular events. The targeted modulation of the endogenous mechanisms of inflammation, rather than its simple suppression, will become key in treating chronic inflammatory diseases. A comprehensive characterization of the signalling molecules involved in inflammation, such as endogenous lipid mediators, is thus needed. Here, we propose a powerful MS-based platform for the simultaneous quantitation of sixty salivary lipid mediators in CVD samples. Saliva, which represents a non-invasive and painless alternative to blood, was collected from patients suffering from acute and chronic heart failure (AHF and CHF, respectively), obesity and hypertension. Of all the patients, those with AHF and hypertension showed higher levels of isoprostanoids, which are key indexes of oxidant insult. Compared to the obese population, AHF patients showed lower levels (p < 0.02) of antioxidant omega-3 fatty acids, in line with the "malnutrition-inflammation complex syndrome" typical of HF patients. At hospital admission, AHF patients showed significantly higher levels (p < 0.001) of omega-3 DPA and lower levels (p < 0.04) of lipoxin B4 than CHF patients, suggesting a lipid rearrangement typical of the failing heart during acute decompensation. If confirmed, our results highlight the potential use of lipid mediators as predictive markers of re-acutisation episodes, thus providing opportunities for preventive intervention and a reduction in hospitalizations.

Bioactive Oxylipins Profile in Marine Microalgae.

Microalgae are photosynthetic microscopic organisms that serve as the primary food source in aquatic environments. Microalgae can synthesize a wide variety of molecules, such as polyunsaturated fatty acids (PUFAs) of the omega-3 and omega-6 series. Oxidative degradation of PUFA due to radical and/or enzymatic conversion leads to the formation of oxylipins, which are compounds known for their bioactive properties. In the present study, we aim to profile oxylipins from five microalgae species grown in 10-L photo-bioreactors under optimal conditions. During their exponential phase, microalgae were harvested, extracted and analyzed by LC-MS/MS to determine the qualitative and quantitative profile of oxylipins for each species. The five different selected microalgae revealed a high diversity of metabolites, up to 33 non-enzymatic and 24 enzymatic oxylipins present in different concentrations. Taken together, these findings highlight an interesting role of marine microalgae as a source of bioactive lipids mediators, which we hypothesize have an important function in preventive health measures such as amelioration of inflammation. The rich mixture of oxylipins may display advantages to biological organisms, especially by providing for human health benefits including antioxidant, anti-inflammatory, neuroprotective or immunomodulator activities. Some oxylipins are also well known for their cardiovascular properties.

Decreased oxidative stress and altered urinary oxylipidome by intravenous omega-3 fatty acid emulsion in a randomized controlled trial of older subjects hospitalized for COVID-19.

Proinflammatory bioactive lipid mediators and oxidative stress are increased in coronavirus disease 2019 (COVID-19). The randomized controlled single-blind trial COVID-Omega-F showed that intravenous omega-3 polyunsaturated fatty acids (n-3 PUFA) shifted the plasma lipid signature of COVID-19 towards increased proresolving precursor levels and decreased leukotoxin diols, associated with a beneficial immunodulatory response. The present study aimed to determine the effects of n-3 PUFA on the urinary oxylipidome and oxidative stress in COVID-19. From the COVID-Omega-F trial, 20 patients hospitalized for COVID-19 had available serial urinary samples collected at baseline, after 24-48 h, and after completing 5 days treatment with one daily intravenous infusion (2 mL/kg) of either placebo (NaCl; n = 10) or a lipid emulsion containing 10 g of n-3 PUFA per 100 mL (n = 10). Urinary eicosanoids and isoprostanes were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Erythrocytes obtained at the different time-points from n = 10 patients (n = 5 placebo and n = 5 n-3 PUFA) were used for determination of reactive oxygen species. Intravenous n-3 PUFA emulsion administration altered eicosanoid metabolites towards decreased levels for mediators of inflammation and thrombosis, and increased levels of the endothelial function mediator prostacyclin. Furthermore, non-enzymatic metabolism was skewed towards n-3 PUFA-derived metabolites with potential anti-inflammatory and pro-resolving effects. The oxidative stress marker 15-F2t-isoprostane was significantly lower in patients receiving n-3 PUFA treatment, who also exhibited significantly decreased erythrocyte oxidative stress compared with placebo-treated patients. These findings point to additional beneficial effects of intravenous n-3 PUFA emulsion treatment through a beneficial oxylipin profile and decreased oxidative stress in COVID-19.

Identification of bacterial lipo-amino acids: origin of regenerated fatty acid carboxylate from dissociation of lipo-glutamate anion.

The identification of bacterial metabolites produced by the microbiota is a key point to understand its role in human health. Among them, lipo-amino acids (LpAA), which are able to cross the epithelial barrier and to act on the host, are poorly identified. Structural elucidation of few of them was performed by high-resolution tandem mass spectrometry based on electrospray combined with selective ion dissociations reach by collision-induced dissociation (CID). The negative ions were used for their advantages of yielding only few fragment ions sufficient to specify each part of LpAA with sensitivity. To find specific processes that help structural assignment, the negative ion dissociations have been scrutinized for an LpAA: the N-palmitoyl acyl group linked to glutamic acid (C16Glu). The singular behavior of [C16Glu-H]¯ towards CID showed tenth product ions, eight were described by expected fragment ions. In contrast, instead of the expected product ions due to CONH-CH bond cleavage, an abundant complementary dehydrated glutamic acid and fatty acid anion pair were observed. Specific to glutamic moiety, they were formed by a stepwise dissociation via molecular isomerization through ion-dipole formation prior to dissociation. This complex dissociated by partner splitting either directly or after inter-partner proton transfer. By this pathway, surprising regeneration of deprotonated fatty acid takes place. Such regeneration is comparable to that occurred from dissociation to peptides containing acid amino-acid. Modeling allow to confirm the proposed mechanisms explaining the unexpected behavior of this glutamate conjugate.

α-Linolenic acid and product octadecanoids in Styrian pumpkin seeds and oils: How processing impacts lipidomes of fatty acid, triacylglycerol and oxylipin molecular structures.

Styrian pumpkin seed oil is a conditioned green-colored oil renowned for nutty smell and taste. Due to α-linolenic acid (ALA) contents below 1% of total fatty acids and the prospect of nutritional health claims based on its potential oxidation products, we investigated the fate of ALA and product oxylipins in the course of down-stream processing of seeds and in oils. Lipidomic analyses with Lipid Data Analyzer 2.8.1 revealed: Processing did not change (1) main fatty acid composition in the oils, (2) amounts of triacylglycerol species, (3) structures of triacylglycerol molecular species containing ALA. (4) Minor precursor ALA in fresh Styrian and normal pumpkins produced 6 product phytoprostanes in either cultivar, quantitatively more in the latter. (5) In oil samples 7 phytoprostanes and 2 phytofurans were detected. The latter two are specific for their presence in pumpkin seed oils, of note, quantitatively more in conditioned oils than in cold-pressed native oils.

Phytoprostanes from Date Palm Fruit and Byproducts: Five Different Varieties Grown in Two Different Locations As Potential sources.

Date palm fruit has been considered for centuries as an ancient nutritional constituent in the human diet. Recently, global trade in dates increased at an average that, simultaneously, will be accompanied by an increase in date palm byproducts. Supported by date phytochemicals and their health benefits, the aim of this work is to evaluate for the first time the presence of special metabolites of plant called phytoprostanes (PhytoPs) in five different varieties of the Phoenix dactylifera L. pulps and pits using a microLC-ESI-QTrap-MS/MS methodology. Results obtained showed the interest of using these matrices as potential sources of several PhytoPs (ent-16-B1-PhytoP; ent-9-L1-PhytoP; and epimers of ent-16-F1t-PhytoP and of 9-F1t-PhytoP). The variation in concentration between different varieties and different DPF parts was also evaluated. Results obtained will help to unravel the biological activities associated with DPF consumption that could be related to these bioactive metabolites.

F4-Neuroprostanes: A Role in Sperm Capacitation.

F4-neuroprostanes (F4-NeuroPs), derived from the oxidative metabolization of docosahexaenoic acid (DHA), are considered biomarkers of oxidative stress in neurodegenerative diseases. Neurons and spermatozoa display a high DHA content. NeuroPs might possess biological activities. The aim of this in vitro study was to investigate the biological effects of chemically synthetized 4-F4t-NeuroP and 10-F4t-NeuroP in human sperm. Total progressive sperm motility (p < 0.05) and linearity (p = 0.016), evaluated by a computer-assisted sperm analyzer, were significantly increased in samples incubated with 7 ng F4-NeuroPs compared to non-supplemented controls. Sperm capacitation was tested in rabbit and swim-up-selected human sperm by chlortetracycline fluorescence assay. A higher percentage of capacitated sperm (p < 0.01) was observed in samples incubated in F4-NeuroPs than in the controls. However, the percentage of capacitated sperm was not different in F4-NeuroPs and calcium ionophore treatments at 2 h incubation. The phosphorylated form of AMPKα was detected by immunofluorescence analysis; after 2 h F4-NeuroP incubation, a dotted signal appeared in the entire sperm tail, and in controls, sperm were labeled in the mid-piece. A defined level of seminal F4-NeuroPs (7 ng) showed a biological activity in sperm function; its addition in sperm suspensions stimulated capacitation, increasing the number of sperm able to fertilize.

Peripancreatic Adipose Tissue Remodeling and Inflammation during High Fat Intake of Palm Oils or Lard in Rats.

Excessive fat consumption leads to the development of ectopic adipose tissues, affecting the organs they surround. Peripancreatic adipose tissue is implicated in glucose homeostasis regulation and can be impaired in obesity. High palm oil consumption's effects on health are still debated. We hypothesised that crude and refined palm oil high-fat feeding may have contrasting effects on peripancreatic adipocyte hypertrophy, inflammation and lipid oxidation compound production in obese rats. In Wistar rats, morphological changes, inflammation and isoprostanoid production following oxidative stress were assessed in peripancreatic adipose tissue after 12 weeks of diets enriched in crude or refined palm oil or lard (56% energy from fat in each case) versus a standard chow diet (11% energy from fat). Epididymal white and periaortic brown adipose tissues were also included in the study. A refined palm oil diet disturbed glucose homeostasis and promoted lipid deposition in periaortic locations, as well as adipocyte hypertrophy, macrophage infiltration and isoprostanoid (5-F2c-isoprostane and 7(RS)-ST-Δ8-11-dihomo-isofuran) production in peripancreatic adipose tissue. Crude palm oil induced a lower impact on adipose deposits than its refined form and lard. Our results show that the antioxidant composition of crude palm oil may have a protective effect on ectopic adipose tissues under the condition of excessive fat intake.

First Total Synthesis of Phytoprostanes with Prostaglandin-Like Configuration, Evidence for Their Formation in Edible Vegetable Oils and Orienting Study of Their Biological Activity.

Phytoprostanes (PhytoP) are natural products, which form in plants under oxidative stress conditions from α-linolenic acid. However, their epimers with relative prostaglandin configuration termed phytoglandins (PhytoG) have never been detected in Nature, likely because of the lack of synthetic reference material. Here, the first asymmetric total synthesis of such compounds, namely of PhytoGF1α (9-epi-16-F1t -PhytoP) and its diastereomer ent-16-epi-PhytoGF1α (ent-9,16-diepi-16-F1t -PhytoP), has been accomplished. The synthetic strategy is based on radical anion oxidative cyclization, copper(I)-mediated alkyl-alkyl coupling and enantioselective reduction reactions. A UHPLC-MS/MS study using the synthesized compounds as standards indicates PhytoG formation at significant levels during autoxidation of α-linolenic acid in edible vegetable oils. Initial testing of synthetic PhytoGs together with F1 -PhytoP and 15-F2t -IsoP derivatives for potential interactions with the PGF2α (FP) receptor did not reveal significant activity. The notion that PUFA-derived oxidatively formed cyclic metabolites with prostaglandin configuration do not form to a significant extent in biological or food matrices has to be corrected. Strong evidence is provided that oxidatively formed PhytoG metabolites may be ingested with plant-derived food, which necessitates further investigation of their biological profile.

Enrichment of alpha-linolenic acid in rodent diet reduced oxidative stress and inflammation during myocardial infarction.

Myocardial infarction (MI) is an irreversible event caused by cardiac ischemia and may be fatal. Studies reported that increased intake of n-3 polyunsaturated fatty acids (PUFA) namely, eicosapentaenoic acid and docosahexaenoic acid reduce the risk of cardiovascular disease and lower the incidence of MI. Nonetheless, the cardioprotective effect of plant n-3-PUFA such as α-linolenic acid (ALA) in the diet is not conclusive. In this study, Sprague Dawley rats were supplemented with isocaloric diets enriched with ALA rich flaxseed (FS) and flaxseed oil (FSO), and normal chow (Control) for 4 weeks. MI was induced by isoproterenol (ISO) injection. Results showed that all ALA-enriched diets displayed cardioprotection against MI. The heart to body weight ratio, plasma LDH activity and plasma cTnI were reduced compared to ISO and was prominent in FS diet. ALA and EPA were up-regulated in both tissues and plasma by ALA-diets compared to Control and remained higher than ISO groups. Notably, LOX-mediated HETEs decreased whereas LOX-mediated HDHAs were elevated in both tissues and plasma of ALA-enriched diets compared to ISO. In addition, non-enzymatic oxidized products from arachidonic acid including 15-F2t-IsoP were reduced in both tissues and plasma of MI rats supplemented with ALA-enriched diets while those from n-3 PUFAs including F4-NeuroPs, PhytoPs and PhytoFs were elevated compared to control. ALA-enriched diets particularly flaxseed reduced gene expressions of inflammatory cytokines namely IL-1ß, IL-6 and TNFα and prevented the down regulation of antioxidant catalase in the heart tissues. In conclusion ALA-enriched diets potentially exerted cardioprotection through the regulation of anti-inflammatory and anti-oxidative mediators from n-3 PUFA autooxidation.

Long chain omega-3 fatty acids and their oxidized metabolites are associated with reduced prostate tumor growth.

INTRODUCTION: Cancer has been associated with increased oxidative stress and deregulation of bioactive oxylipins derived from long-chain polyunsaturated fatty acids (LC-PUFA) like arachidonic acid (AA). There is a debate whether ω-3 LC-PUFA could promote or prevent prostate tumor growth through immune modulation and reduction of oxidative stress. Our aim was to study the association between enzymatically or non-enzymatically produced oxidized-LC-PUFA metabolites and tumor growth in an immune-competent eugonadal and castrated C57BL/6 male mice injected with TRAMP-C2 prostate tumor cells, fed with ω-3 or ω-6 LC-PUFA-rich diets. MATERIALS AND METHODS: Tumor fatty acids were profiled by gas chromatography and 26 metabolites derived from either AA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were assessed by liquid chromatography-mass spectrometry. RESULTS: The enriched ω-3 diet did not reduce oxidative stress overall in tumors but favored the formation of ω-3 rather than ω-6 derived isoprostanoids. We discovered that EPA and its oxidized-derivatives like F3-isoprostanes and prostaglandin (PG)F3α, were inversely correlated with tumor volume (spearman correlations and T-test, p<0.05). In contrast, F2-isoprostanes, adrenic acid, docosapentaenoic acid (DPAω-6) and PGE2 were positively correlated with tumor volume. Interestingly, F4-neuroprostanes, PGD2, PGF2α, and thromboxane were specifically increased in TRAMP-C2 tumors of castrated mice compared to those of eugonadal mice. DISCUSSION: Decreasing tumor growth under ω-3 diet could be attributed in part to increased levels of EPA and its oxidized-derivatives, a reduced level of pro-angiogenic PGE2 and increased levels of F4-neuroprostanes and resolvins content in tumors, suspected of having anti-proliferative and anti-inflammatory effects.

Chemical Compositional Changes in Over-Oxidized Fish Oils.

A recent study has reported that the administration during gestation of a highly rancid hoki liver oil, obtained by oxidation through sustained exposure to oxygen gas and incident light for 30 days, causes newborn mortality in rats. This effect was attributed to lipid hydroperoxides formed in the omega-3 long-chain polyunsaturated fatty acid-rich oil, while other chemical changes in the damaged oil were overlooked. In the present study, the oxidation condition employed to damage the hoki liver oil was replicated, and the extreme rancidity was confirmed. A detailed analysis of temporal chemical changes resulting from the sustained oxidative challenge involved measures of eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) omega-3 oil oxidative quality (peroxide value, para-anisidine value, total oxidation number, acid value, oligomers, antioxidant content, and induction time) as well as changes in fatty acid content, volatiles, isoprostanoids, and oxysterols. The chemical description was extended to refined anchovy oil, which is a more representative ingredient oil used in omega-3 finished products. The present study also analyzed the effects of a different oxidation method involving thermal exposure in the dark in contact with air, which is an oxidation condition that is more relevant to retail products. The two oils had different susceptibility to the oxidation conditions, resulting in distinct chemical oxidation signatures that were determined primarily by antioxidant protection as well as specific methodological aspects of the applied oxidative conditions. Unique isoprostanoids and oxysterols were formed in the over-oxidized fish oils, which are discussed in light of their potential biological activities.

Lactobacillus rhamnosus GG and Oat Beta-Glucan Regulated Fatty Acid Profiles along the Gut-Liver-Brain Axis of Mice Fed with High Fat Diet and Demonstrated Antioxidant and Anti-Inflammatory Potentials.

SCOPE: This study takes a novel approach to investigate the anti-inflammatory and antioxidant effects of prebiotic oat beta-glucan (OAT) and the probiotic Lactobacillus rhamnosus GG (LGG) against high-fat diets (HFD) by examining the fatty acid profiles in the gut-liver-brain axis. METHOD AND RESULTS: HFD-fed C57BL/6N mice are supplemented with OAT and/or LGG for 17 weeks. Thereafter, mass spectrometry-based targeted lipidomics is employed to quantify short-chain fatty acids (SCFA), polyunsaturated fatty acids (PUFA), and oxidized PUFA products in the tissues. Acetate levels are suppressed by HFD in all tissues but reversed in the brain and liver by supplementation with LGG, OAT, or LGG + OAT, and in cecum content by LGG. The n-6/n-3 polyunsaturated fatty acid (PUFA) ratio is elevated by HFD in all tissues but is lowered by LGG and OAT in the cecum and the brain, and by LGG + OAT in the brain, suggesting the anti-inflammatory property of LGG and OAT. LGG and OAT synergistically, but not individually attenuate the increase in non-enzymatic oxidized products, indicating their synbiotic antioxidant property. CONCLUSION: The regulation of the fatty acid profiles by LGG and OAT, although incomplete, but demonstrates their anti-inflammatory and antioxidant potentials in the gut-liver-brain axis against HFD.

Oxylipin regulation by phenolic compounds from coffee beverage: Positive outcomes from a randomized controlled trial in healthy adults and macrophage derived foam cells.

Oxylipins are considered biomarkers related to cardiovascular diseases (CVDs). They are generated in vivo via the oxygenation of polyunsaturated fatty acids as a result of oxidative stress and inflammation. Oxylipins are involved in vascular functions and are produced during foam cell formation in atherogenesis. Additionally, the consumption coffee is associated with the regulation on a particular oxylipin group, the F2t-isoprostanes (F2t-IsoPs). This function has been attributed to the chlorogenic acids (CGAs) from the coffee beverage. Considering the anti-inflammatory and antioxidant properties of CGAs, we evaluated the effects of two types of coffee that provided 787 mg CGAs/day (Coffee A) and 407 mg CGAs/day (Coffee B) by reducing 35 selected oxylipins in healthy subjects. Furthermore, we assessed the effect of CGAs on the cellular proatherogenic response in foam cells by using an oxidized LDL (oxLDL)-macrophage interaction model. After eight weeks of coffee consumption, the contents of 12 urine oxylipins were reduced. However, the effect of Coffee A showed a stronger decrease in IsoPs, dihomo-IsoPs, prostaglandins (PGs) and PG metabolites, probably due to its higher content of CGAs. Neither of the two coffees reduced the levels of oxLDL. Moreover, the in vitro oxylipin induction by oxLDL on foam cells was ameliorated by phenolic acids and CGAs, including the inhibition of IsoPs and PGs by caffeoylquinic and dicaffeoylquinic acids, respectively, while the phenolic acids maintained both antioxidant and anti-inflammatory activities. These findings suggest that coffee antioxidants are strong regulators of oxylipins related to CVDs. The clinical trial was registered on the International Clinical Trials Registry Platform, WHO primary registry (RPCEC00000168).

Evaluation of Phoenix dactylifera Edible Parts and Byproducts as Sources of Phytoprostanes and Phytofurans.

Even though traditionally date-fruit has been featured by a marginal use, mainly restricted to its dietary intake, in recent years, it has raised the range of applications for this agro-food production. These new uses have entailed an enlarged production of date fruits and, simultaneously, of date palm byproducts. Encouraged by the traditional medicinal uses of dates, according to their phytochemical composition, the present work was focused on the evaluation of a new family of secondary metabolites, the plant oxylipins phytoprostanes (PhytoPs) and phytofurans (PhytoFs), in six separate matrixes of the date palm edible parts and byproducts, applying an UHPLC-ESI-QqQ-MS/MS-based methodology. The evaluation for the first time of date palm edible parts and byproducts as a dietary source of PhytoPs and PhytoFs provides evidence on the value of six different parts (pulp, skin, pits, leaves, clusters, and pollen) regarding their content in these plant oxylipins evidenced by the presence of the PhytoPs, 9-F1t-PhytoP (201.3-7223.1 ng/100 g dw) and 9-epi-9-F1t-PhytoP (209.7-7297.4 ng/100 g dw), and the PhytoFs ent-16(RS)-9-epi-ST-Δ14-10-PhytoF (4.6-191.0 ng/100g dw), and ent-16(RS)-13-epi-ST-Δ14-9-PhytoF as the most abundant compounds. Regarding the diverse matrixes assessed, pollen, clusters, and leaves for PhytoPs and skins and pollen for PhytoFs were identified as the most interesting sources of these compounds. In this concern, the information obtained upon the detailed characterization performed in the present work will allow unravelling the biological interest of PhytoPs and PhytoFs and the extent to which these compounds could exert valuable biological activities upon in vitro (mechanistic) and in vivo studies, allocating the effort-focus on the chemical species of PhytoPs and PhytoFs responsible for such traits.

Effects of Deficit Irrigation, Rootstock, and Roasting on the Contents of Fatty Acids, Phytoprostanes, and Phytofurans in Pistachio Kernels.

Pistachio (Pistacia vera L.) is a drought-tolerant species grown under the semiarid conditions of the Mediterranean basin. For this reason, it is essential to make an exhaustive quantification of yield and quality benefits of the kernels because the regulated deficit irrigation will allow significant water savings with a minimum impact on yield while improving kernel quality. The goal of this scientific work was to study the influence of the rootstock, water deficit during pit hardening, and kernel roasting on pistachio (P. vera, cv. Kerman) fruit yield, fruit size, and kernel content of fatty acids phytoprostanes (PhytoPs) and phytofurans (PhytoFs) for the first time. Water stress during pit hardening did not affect the pistachio yield. The kernel cultivar showed a lower oleic acid and a higher linoleic acid contents than other cultivars. Kernels from plants grafted on the studied rootstocks showed very interesting characteristics. P. integerrima led to the highest percentage of monounsaturated fatty acids. Regarding the plant oxylipins, P. terebinthus led to the highest contents of PhytoPs and PhytoFs (1260 ng/100 g and 16.2 ng/100 g, respectively). In addition, nuts from trees cultivated under intermediate water deficit during pit hardening showed increased contents of the 9-series F1-phytoprostanes and ent-16(RS)-9-epi-ST-Δ14-10-phytofuran. However, roasting of pistachios led to PhytoP degradation. Therefore, plant cultivar, deficit irrigation, rootstock, and roasting must be considered to enhance biosynthesis of these secondary metabolites. New tools using agricultural strategies to produce hydroSOS pistachios have been opened thanks to the biological properties of these prostaglandin-like compounds linking agriculture, nutrition, and food science technology for further research initiatives.

Characterization and modulation of brain lipids content of rainbow trout fed with 100% plant based diet rich in omega-3 long chain polyunsaturated fatty acids DHA and EPA.

Brain functions are known to be mainly modulated by adequate dietary intake. Inadequate intake as can be an excess or significant deficiency affect cognitive processes, behavior, neuroendocrine functions and synaptic plasticity with protective or harmful effects on neuronal physiology. Lipids, in particular, ω-6 and ω-3 long chain polyunsaturated fatty acids (LC-PUFAs) play structural roles and govern the different functions of the brain. Hence, the goal of this study was to characterize the whole brain fatty acid composition (precursors, enzymatic and non-enzymatic oxidation metabolites) of fish model of rainbow trout fed with three experimental plant-based diet containing distinct levels of eicosapentaenoic acid (EPA, 20:5 ω-3) and docosahexaenoic acid (DHA, 22:6 ω-3) (0% for low, 15.7% for medium and 33.4% for high, total fatty acid content) during nine weeks. Trout fed with the diet devoid of DHA and EPA showed reduced brain content of total ω-3 LC-PUFAs, with diminution of EPA and DHA. Selected enzymatic (cyclooxygenases and lipoxygenases) oxidation metabolites of arachidonic acid (AA, 20:4 ω-6) decrease in medium and high ω-3 LC-PUFAs diets. On the contrary, total selected enzymatic oxidation metabolites of DHA and EPA increased in high ω-3 LC-PUFAs diet. Total selected non-enzymatic oxidation metabolites of DHA (not detected for EPA) increased in medium and high ω-3 LC-PUFAs diets. In conclusion, this work revealed for the first time in fish model the presence of some selected enzymatic and non-enzymatic oxidation metabolites in brain and the modulation of brain lipid content by dietary DHA and EPA levels.