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Oxidized low-density lipoprotein (oxLDL) is a well-recognized proatherogenic particle that functions in atherosclerosis. In this study, we established conditions to generate human oxLDL, characterized according to the grade of lipid and protein oxidation, particle size and oxylipin content. The induction effect of the cellular proatherogenic response was assessed in foam cells by using an oxLDL-macrophage interaction model. Uptake of oxLDL, reactive oxygen species production and expression of oxLDL receptors (CD36, SR-A and LOX-1) were significantly increased in THP-1 macrophages. Analyses of 35 oxylipins revealed that isoprostanes (IsoP) and prostaglandins (PGs) derived from the oxidation of arachidonic, dihomo gamma-linolenic and eicosapentaenoic acids were strongly and significantly induced in macrophages stimulated with oxLDL. Importantly, the main metabolites responsible for the THP1-macrophage response to oxLDL exposure were the oxidative stress markers 5-epi-5-F 2t -IsoP, 15-E 1t -IsoP, 8-F 3t -IsoP and 15-keto-15-F 2t -IsoP as well as inflammatory markers PGDM, 17-trans-PGF 3α , and 11β-PGF 2α , all of which are reported here, for the first time, to function in the interaction of oxLDL with THP-1 macrophages. By contrast, a salvage pathway mediated by anti-inflammatory PGs (PGE 1 and 17-trans-PGF 3α ) was also identified, suggesting a response to oxLDL-induced injury. In conclusion, when THP-1 macrophages were treated with oxLDL, a specific induction of biomarkers related to oxidative stress and inflammation was triggered. This work contributes to our understanding of initial atherogenic events mediated by oxLDL-macrophage interactions and helps to generate new approaches for their modulation., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

One of the most promising approaches to confront the complexity of central nervous system disorders are new multi-target directed ligands (MTDLs). Five medicinal species (Cereus grandiflorus (L.) Mill., Hyssopus officinalis L., Acorus calamus L., Silybum marianum L. Gaertn. and Turnera diffusa Willd. Ex Schult), selected for their ethnopharmacological relevance, were object for in vitro screening. The aqueous extract of T. diffusa revealed the strongest neuroactive potential, inhibiting monoamine oxidase-A (IC 50  = 129.80 ± 11.97 μg/mL), and acetyl- and butyrylcholinesterase (IC 25  = 0.352 ± 0.011 and 0.370 ± 0.036 mg/mL, respectively). Its phenolic profile was established for the first time by HPLC-DAD-ESI/MS n . Twenty-six out of thirty-seven compounds were newly identified in this species. The pre-treatment with this flavonoid-rich extract promoted a rightward shift of the glutamate concentration neuronal cell (SH-SY5Y) death response curve. Furthermore, it significantly reduced the early phase formation of intracellular reactive species after glutamate and t-BHP exposure, suggesting that neuroprotection in SH-SY5Y cells was, in part, mediated by antioxidant mechanisms., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We analyzed biomarkers of lipid peroxidation of the nervous system -F 2 -dihomo-isoprostanes, F 3 -neuroprostanes, and F 4 -neuroprostanes- in urine samples from 158 healthy volunteers ranging from 4 to 88 years old with the aim of analyzing possible associations between their excretion values and age (years). Ten biomarkers were screened in the urine samples by UHPLC-QqQ-MS/MS. Four F 2 -dihomo-isoprostanes (ent-7-(R)-7-F 2t -dihomo-isoprostane, ent-7-epi-7-F 2t -dihomo-isoprostane, 17-F 2t- dihomo-isoprostane, 17-epi-17-F 2t -dihomo-isoprostane), and one DPA-neuroprostane (4-F 3t -neuroprostane) were detected in the samples. On the one hand, we found a significant, positive correlation (Rho: 0.197, P=0.015) between the age increase and the amount of total F 2 -dihomo-IsoPs. On the other hand, the values were significantly higher in the childhood group (4-12 years old), when compared to the adolescence group (13-17 years old) and the young adult group (18-35 years old). Surprisingly, no significant differences were found between the middle-aged adults (36-64 years old) and the elderly adults (65-88 years old). We display a snapshot situation of excretory values of oxidative stress biomarkers of the nervous system, using healthy volunteers representative of the different stages of human growth and development. The values reported in this study could be used as a basal or starting point in clinical interventions related to aging processes and/or pathologies associated with the nervous system., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

F 4 -neuroprostanes, F 3 -neuroprostanes n-6 DPA , and F 2 -dihomo-isoprostanes, metabolites of non-enzymatic lipid peroxidation of polyunsaturated fatty acids [docosahexaenoic acid, n-6 docosapentanoic acid, and adrenic acid respectively], have become important biomarkers for oxidative stress in several diseases like epilepsy and alzheimer. These biomarkers and the 15-F 2t -isoprostane (also known as 8-iso-PGF 2α ) , a F 2 -isoprostane isomer measured as reference oxidative marker at systemic level, were analyzed by UHPLC-QqQ-MS/MS in the urine of 60 renal recipients from cadaveric donors of the Nephrology Unit of the University Hospital Virgen de la Arrixaca, at six different times during the first six months after renal transplantation, and were compared with a control group of 60 healthy subjects from the same hospital. A total of 11 metabolites were analyzed and different patterns were observed. A tendency to decrease was observed in three metabolites (4-epi-4-F 3t - NeuroP n-6 DPA , ent-7(RS)-7-F 2t -dihomo-IsoP, and ent-7(S)-7-F 2t -dihomo-IsoP) and in our reference oxidative marker (15-F 2t -IsoP) when kidney function improved and the excretion of urine proteins decreased. These results suggest that these three biomarkers of oxidative stress could be useful to assess renal function in the postransplant phase. Unfortunately, little is known about this kind of biomarker in this cohort of patients, so further investigation would be required in the clinical field to clarify the relationship between oxidative stress and the graft function, as well as the usefulness of these biomarkers as rejection markers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of the this study was to determine the effect of a polyphenols-rich juice (aronia-citrus juice, ACJ) on F 4 -neuroprostanes and F 2 -dihomo-isoprostanes-markers of oxidative stress associated with the central nervous system (CNS)-in 16 elite triathletes under a controlled diet for triathlon training (145 days). In the triathletes, a decrease of the lipid peroxidation markers after ACJ intake, associated with neuronal membrane degradation (10-epi-10-F 4t -neuroprostane and 10-F 4t -neuroprostane), was observed when compared with placebo stage values. Regarding the F 2 -dihomo-isoprostanes, a significant decrease of the neuromotor system damage biomarkers (17-F 2t -dihomo-isoprostane) with an increase of training load during the study was observed, although the decrease of the load training at the last stage showed a significant increase of the values of ent-7-(RS)-7-F 2t -dihomo-IsoP, suggesting a possible role in adaptation post-training. On the other hand, the changes in the excretion of 17-epi-17-F 2t -dihomo-IsoP provided a positive connection between physical exercise and ACJ intake. Thus, the results showed in this clinical study in young triathletes will help to elucidate novel interactions and mechanisms between the excretion of lipid peroxidation metabolites from CNS, supplementation of polyphenols-rich juice in the diet and physical exercise during a training season.

This randomized and controlled trial investigated whether the increase in elite training at different altitudes altered the oxidative stress biomarkers of the nervous system. This is the first study to investigate four F4-neuroprostanes (F4-NeuroPs) and four F2-dihomo-isoprostanes (F2-dihomo-IsoPs) quantified in 24-h urine. The quantification was carried out by ultra high pressure liquid chromatography-triple quadrupole-tandem mass spectrometry (UHPLC-QqQ-MS/MS). Sixteen elite triathletes agreed to participate in the project. They were randomized in two groups, a group submitted to altitude training (AT, n = 8) and a group submitted to sea level training (SLT) (n = 8), with a control group (Cg) of non-athletes (n = 8). After the experimental period, the AT group triathletes gave significant data: 17-epi-17-F2t-dihomo-IsoP (from 5.2 ± 1.4 μg/mL 24 h(-1) to 6.6 ± 0.6 μg/mL 24 h(-1)), ent-7(RS)-7-F2t-dihomo-IsoP (from 6.6 ± 1.7 μg/mL 24 h(-1) to 8.6 ± 0.9 μg/mL 24 h(-1)), and ent-7-epi-7-F2t-dihomo-IsoP (from 8.4 ± 2.2 μg/mL 24 h(-1) to 11.3 ± 1.8 μg/mL 24 h(-1)) increased, while, of the neuronal degeneration-related compounds, only 10-epi-10-F4t-NeuroP (8.4 ± 1.7 μg/mL 24 h(-1)) and 10-F4t-NeuroP (5.2 ± 2.9 μg/mL 24 h(-1)) were detected in this group. For the Cg and SLT groups, no significant changes had occurred at the end of the two-week experimental period. Therefore, and as the main conclusion, the training at moderate altitude increased the F4-NeuroPs- and F2-dihomo-isoPs-related oxidative damage of the central nervous system compared to similar training at sea level.

Current evidence supports the positive association between the consumption of plant foods and health. In this work, we assessed the effect of consuming a half-serving (30 g) or one serving (60 g) of broccoli sprouts on the urinary concentrations of biomarkers of oxidative stress (isoprostanes) and inflammation (prostaglandins and thromboxanes). Twenty-four volunteers participated in the project. A quantitative determination of sulforaphane and its mercapturic derivatives, eicosanoids, and total vitamin C in urine was performed. The intake of broccoli sprouts produced an increase in the urinary concentrations of sulforaphane metabolites and vitamin C. Among the 13 eicosanoids analyzed, tetranor-PGEM and 11β-PGF2α as well as 11-dehydro-TXB2 showed a significant decrease in their urinary concentrations after the ingestion of broccoli sprouts. Therefore, the consumption of broccoli sprouts modulated the excretion of biomarkers linked to inflammation and vascular reactions without exerting a significant influence on the oxidation of phospholipids in vivo., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The present study aimed to discover the effects of exogenously foliar-applied salicylic acid (SA) in concentrations of 0, 1 and 15 mM (applied 7 and 21 days after heading) on oxidative stress. The effects were monitored through the concentrations of phytoprostanes (PhytoPs) and phytofurans (PhytoFs) in immature and mature grains of three genotypes of rice ('R52', 'R45' and 'Yerua'), and their influence on grains per panicle and chalkiness. Chromatographic separation of PhytoPs and PhytoFs was performed using a UHPLC coupled to triple quadrupole-MS/MS (Agilent Technologies, Germany). The concentrations of oxylipins showed differences in both harvest times (immature and mature) for each genotype. The advanced lines, 'R52' and 'R45', showed concentrations that were 24.0 and 79.0% lower than those of the immature grains, respectively. The PhytoFs concentration in "R45" was 46.0% lower in the mature grains. In unripe grains, SA reduced a single oxylipin of all those analyzed, while in mature grains, a significant decrease in six of the ten monitored biomarkers was observed. The SA produced an increase in grains per panicle, and a decrease in chalkiness. Therefore, salicylic acid-mediated antioxidant regulatory capacities due to oxylipin down-regulation could favor grain filling and, hence, rice production. [ABSTRACT FROM AUTHOR]

Oxylipins, lipid biomarkers of inflammation are considered the gold standard method to evaluate the inflammatory and antioxidant status. The aim of the present study was to investigate whether the administration of a polyphenolic extract shot in the form of a nutraceutical was able to reduce inflammation, measured in urine markers. Ninety-two participants (45 males, 47 females, age 34 ± 11 years, weight 73.10 ± 14.29 kg, height 1.72 ± 9 cm, BMI 24.40 ± 3.43 kg/m2) completed the study after an intervention of two 16-week periods consuming extract or placebo separated by a 4-week washout period. The results showed significant differences in terms of reduction of different pro-inflammatory oxylipins (15-keto-PGF2α (from 0.90 ± 0.25 ng/mL to 0.74 ± 0.19 ng/mL p < 0.05), ent-PGF2α (from 1.59 ± 0.37 ng/mL to 1.44 ± 0.32 ng/mL p < 0.05), 2,3-dinor-15-F2t-Isop) (from 1.17 ± 0.35 ng/mL to 1.02 ± 0.27 ng/mL p < 0.05), in total oxylipins count (from 8.03 ± 1.86 ng/mL to 7.25 ± 1.23 ng/mL p < 0.05), and increase in PGE2 (from 1.02 ± 0.38 ng/mL to 1.26 ± 0.38 ng/mL p < 0.05) which has an anti-inflammatory character, after extract consumption compared to placebo. The available data seem to indicate that long-term consumption of a nutraceutical with high polyphenol content improves inflammation and oxidation parameters measured in urine, through UHPLC-QqQ-ESI-MS/MS. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The bark of Trichilia catigua A. Juss. (Meliaceae), popularly known as “big catuaba”, is traditionally used in Brazilian folk medicine for its neuroactive potential as memory stimulant, and antinociceptive and antidepressant effects. Aim of the study To study the aqueous extract of T. catigua bark as dual inhibitor of monoamine oxidase A (MAO-A) and acetylcholinesterase (AChE). To explore its antioxidant potential through interaction with xanthine/xanthine oxidase (X/XO) pathway, and to attempt a relationship between its phenolic profile and effects displayed. Materials and methods Phenolic profiling was achieved by HPLC-DAD-ESI / MS n and UPLC-ESI-QTOF-MS analyses. The capacity to inhibit h MAO-A was assessed in vitro , as was that for AChE, evaluated in rat brain homogenates. The direct inhibition of the X/XO pathway and the scavenging of superoxide anion radical were the selected in vitro models to explore the antioxidant potential. The cytotoxic effects were assayed in the human neuronal SH-SY5Y cells by MTT reduction, after direct exposure (24 h). Results Twenty-six compounds were identified and quantified (551.02 ± 37.61 mg/g of lyophilized extract). The phenylpropanoid substituted flavan-3-ols were the most representative compounds (~81% of quantified mass). The extract inhibited h MAO activity in a concentration-dependent manner (IC 50 = 121.06 ± 2.13 μg/mL). A mixed model of inhibition of AChE activity was observed, reflected by the pronounced increase of K m values and a more discreet effect over the V max parameters, calculated from Michaelis-Menten fitted equations. In addition, it was demonstrated that the extract directly inhibits the X/XO pathway (IC 50 = 121.06 ± 2.13 μg/mL) and also imbalances the oxidative stress acting as superoxide anion radical scavenger (EC 50 = 104.42 ± 10.67 μg/mL), an oxidative by-product of this reaction. All these neuroprotective and neurotrophic effects were displayed within the non-toxic range of concentrations (0.063–0.500 μg/mL) in SH-SY5Y cells. Conclusions Our results validate the traditional use of T. catigua bark for its neuroactive and neuroprotective potential. A novel approach upon its application towards the management of neurodegenerative and related symptomatology was likewise demonstrated. [ABSTRACT FROM AUTHOR]

The use of " Mexican calea " (Calea zacatechichi Schltdl.) in ritualistic ceremonies, due to its dream-inducing effects, was until recently limited to indigenous communities in Mexico. However, the plant has recently gained popularity in Western societies being commonly used in recreational settings. Despite the traditional and recreational uses, mechanisms underlying its reported oneirogenic effects remain unknown, with no data available on its neurotoxic profile. The scarcity of toxicological data and the unknown role of major neurotransmitter systems in the dream-inducing properties of the plant prompted us to investigate which neurotransmitters might be affected upon its consumption, as well as the potential cytotoxic effects on neurons and microglial cells. Furthermore, we aimed to explore a relationship between the recorded effects and specific constituents. Effects on cholinergic and monoaminergic pathways were investigated using enzymatic assays, with the latter also being conducted in neuronal SH-SY5Y cells along with the impact on glutamate-induced excitotoxicity. Investigation of the neurotoxic profile was approached in neuronal SH-SY5Y and microglial BV-2 cells, evaluating effects on metabolic performance and membrane integrity using MTT and LDH leakage assays, respectively. Potential interference with oxidative stress was monitored by assessing free radical's levels, as well as 5-lipoxygenase mediated lipid peroxidation. Phenolic constituents were identified through HPLC-DAD-ESI(Ion Trap)MSn analysis. Based on the significant inhibition upon acetylcholinesterase (p < 0.05) and tyrosinase (IC 50 = 60.87 ± 7.3 μg/mL; p < 0.05), the aqueous extract obtained from the aerial parts of C. zacatechichi interferes with the cholinergic and dopaminergic systems, but has no impact against monoamine oxidase A. Additionally, a notable cytotoxic effect was observed in SH-SY5Y and BV-2 cells at concentrations as low as 125 and 500 μg/mL (p < 0.05), respectively, LDH leakage suggesting apoptosis may occur at these concentrations, with necroptosis observed at higher ones. Despite the neurocytotoxic profile, these effects appear to be independent of radical stress, as the C. zacatechichi extract scavenged nitric oxide and superoxide radicals at concentrations as low as 62.5 μg/mL, significantly inhibiting also 5-lipoxygenase (IC 50 = 72.60 ± 7.3 μg/mL; p < 0.05). Qualitative and quantitative analysis using HPLC-DAD-ESI(Ion Trap)MSn enabled the identification of 28 constituents, with 24 of them being previously unreported in this species. These include a series of dicaffeoylquinic, caffeoylpentoside, and feruloylquinic acids, along with 8 flavonols not previously known to occur in the species, mainly 3- O -monoglycosylated derivatives of quercetin, kaempferol, and isorhamnetin. Our findings regarding the neuroglial toxicity elicited by C. zacatechichi emphasize the necessity for a thorough elucidation of the plant's toxicity profile. Additionally, evidence is provided that the aerial parts of the plant inhibit both acetylcholinesterase and tyrosinase, potentially linking its psychopharmacological effects to the cholinergic and dopaminergic systems, with an apparent contribution from specific phenolic constituents previously unknown to occur in the species. Collectively, our results lay the groundwork for a regulatory framework on the consumption of C. zacatechichi in recreational settings and contribute to elucidating previous contradictory findings regarding the mechanisms underlying the dream-inducing effects of the plant. [Display omitted] • First report on the cytotoxicity of Calea zacatechichi in SH-SY5Y and BV-2 cells. • Calea zacatechichi induces neurotoxicity with loss of membrane integrity. • Neuromodulatory effects via inhibiting cholinergic and dopaminergic pathways. • Identification of 24 previously unreported compounds in Calea zacatechichi. • Rutin, 4,5-diCQA, 3,5-diCQA and nictoflorin identified as major compounds. [ABSTRACT FROM AUTHOR]

Cardiometabolic disease risk factors, including obesity, insulin resistance, high blood pressure, and dyslipidemia, are associated with elevated oxidative stress biomarkers like oxylipins. Increased adiposity by itself induces various isomers of this oxidized lipid family, while dietary polyphenols show benefits in its regulation. Previously, we showed that specific co-abundant microorganisms characterized the gut microbiota of Colombians and associated differentially with diet, lifestyle, obesity, and cardiometabolic health status, which led us to hypothesize that urinary oxylipins would reflect the intensity of oxidative metabolism linked to gut microbiota dysbiosis. Thus, we selected a convenience sample of 105 participants (age: 40.2 ± 11.9 years, 47.6% women), grouped according to microbiota, cardiometabolic health status, and body mass index (BMI); and evaluated 33 urinary oxylipins by HPLC-QqQ-MS/MS (e.g., isoprostanes, prostaglandins, and metabolites), paired with anthropometry and blood chemistry information and dietary antioxidants estimated from a 24-h food recall. In general, oxylipins did not show differences among individuals who differed in gut microbiota. While the unmetabolized oxylipin levels were not associated with BMI, the total content of oxylipin metabolites was highest in obese and cardiometabolically abnormal subjects (e.g., insulin resistant), mainly by prostaglandin-D (2,3-dinor-11β-PGF 2α) and 15-F 2t -IsoPs (2,3-dinor-15-F 2t -IsoP and 2,3-dinor-15- epi -15-F 2t -IsoP) metabolites. The total polyphenol intake in this cohort was 1070 ± 627 mg/day. After adjusting for body weight, the polyphenol intake was significantly higher in lean than overweight and showed an inverse association with dinor-oxylipin levels in principal component analysis. These results suggest that the 2,3-dinor-oxylipins could be more specific biomarkers associated with BMI than their parent oxylipins and that are sensitive to be regulated by dietary antioxidants. [Display omitted] • 2,3-dinor oxylipin metabolites excretion is associated with BMI and cardiometabolic health status. • Compared to lean, overweight individuals excrete higher levels of 2,3-dinor oxylipin metabolites. • Dietary antioxidants were higher in lean than overweight individuals and inversely associated with 2,3 dinor-oxylipin metabolites excretion. [ABSTRACT FROM AUTHOR]

Oxylipins such as isoprostanes (IsoPs), prostaglandins (PGs) and thromboxanes (TXs) are lipid mediators derived from the oxidation of polyunsaturated fatty acids, which regulate the magnitude of oxidative stress and inflammation processes and play an important role in pathophysiological processes in the kidney. A total of 36 oxylipins were analyzed by UHPLC-QqQ-MS/MS in the urine of 41 renal recipients from cadaveric donors of the Nephrology Unit of the University Hospital Virgen de la Arrixaca during the first six months after renal transplantation, in order to investigate several candidate oxylipins as more accurate and predictive biomarkers in renal transplantation than classical biological variables. A decrease in nine PGs, mostly from the AA-D pathway (p < 0.05) and one IsoP: 15-keto-15-F 2t -IsoP (p < 0.001) was observed. Moreover, two PGs (2,3-dinor-11β-PGF 2α and 17-trans-PGF 3α) increased between five days and six months after renal transplantation (p < 0.05). In addition, when kidney function improved, a positive correlation between oxylipin levels and the excretion of urine proteins was observed. These results suggest that oxylipins could be useful markers for monitoring renal function in the post-renal transplantation period. These findings could be of utility not only for the development of strategies for long-term preservation of graft function, but also for innovative and alternative therapies -using oxylipins as predictive markers-to avoid organ rejection. Image 1 • Oxylipins (IsoPs, PGs and TXs) were assessed in renal recipients. • Changes in oxylipin levels during the first six months after renal transplantation. • Nine oxylipins decreased as kidney function improved. • A positive correlation between oxylipins and proteinuria was observed. [ABSTRACT FROM AUTHOR]

Highlights • First report of the occurrence of phytoprostanes and phytofurans in cocoa beans. • The profiles of phytoprostanes and phytofurans varied according to the clone. • Content of PUFAs were related to the amounts of phytoprostanes and phytofurans. Abstract Cocoa has been widely discussed as a bioactive food rich in sensory stimulation and health benefits. However, no information has been provided concerning phytoprostanes (PhytoPs) and phytofurans (PhytoFs) in cocoa. These compounds are of interest because they play a role in the regulation of immune function. The present study included 31 cocoa clones. The PhytoPs and PhytoFs were quantified by UHPLC-QqQ-MS/MS. The total PhytoPs and PhytoFs contents ranged from 221.46 to 1589.83 ng g−1 and from 1.18 to 13.13 ng g−1, respectively. The profiles of the PhytoPs and PhytoFs identified in the cocoa beans showed significant differences among the clones analysed. The results indicate that dry fermented cocoa beans are rich in PhytoPs and PhytoFs, which may represent an additional benefit of the consumption of foods derived from cocoa. [ABSTRACT FROM AUTHOR]

The thermal processing of almond kernels implies the use of techniques that produce chemical changes such as oxidation. Phytoprostanes (PhytoPs) are considered biomarkers of the oxidative stress in plants. We studied the PhytoP profile in kernels of almond cultivars under different conditions, in relation to packaging, temperature and time of storage and processing. The most abundant PhytoP was the F 1t series. The PhytoP levels increased significantly with the time of storage (3 and 6 months) and the total PhytoP concentration was higher under air than in a vacuum packaging atmosphere. Storage at 24 °C raised the concentrations of individual PhytoPs and the total sum of PhytoPs. The frying and roasting processes led to a strong reduction of the original concentration of most PhytoPs and promoted the synthesis of specific PhytoPs that were not detected in raw kernels and thus could be biomarkers of the degree of oxidative degradation of almonds. [ABSTRACT FROM AUTHOR]

Oxidative stress is a biochemical state in which reactive oxygen species are generated and it has been associated with pathological states including epilepsy. Therein, neuroprostanes (NeuroPs) and dihomo-isoprostanes (Dihomo-IsoPs)—a series of compounds formed nonenzymatically through free radical-induced DHA, n-6 DPA, and AdA peroxidation–are implicated in the pathophysiological status of various human neurological diseases. A new, robust, and selective analytical method for the determination of 10 NeuroPs/Dihomo-IsoPs in human urine, using solid-phase extraction and UHPLC–QqQ–MS/MS in the multiple reaction monitoring mode (using a negative electrospray ionization interface), was developed. Nine NeuroPs/Dihomo-IsoPs were identified in 15 epileptic patients, matched with healthy volunteers. Among them, 17-F 2t -Dihomo-IsoP, Ent-7( R )-7-F 2t -Dihomo-IsoP, and Ent -7- epi -7-F 2t -Dihomo-IsoP, derived from adrenic acid (AdA), were significantly higher in epileptic patients than in healthy volunteers. The validated method provided a high-throughput assay with a limit of detection and limit of quantification for each analyte of 0.10–5.90 ng mL −1 and 0.15–11.81 ng mL −1 , respectively. The intra- and interday variations were lower than 14%. Dihomo-IsoPs have been considered as potential markers of epilepsy for the first time and their measurement may increase the understanding of the role of oxidative stress in neurological diseases, in intra vitam studies. The present study highlights a potential role of Dihomo-IsoPs as biomarkers in persons with epilepsy, though its mechanisms and possible implications should be the subject of further investigations. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hydroxytyrosol (HT) and its lipophenolic derivatives actively participate in the redox balance of THP-1 cells. • HT and HT-lipophenols have specific anti-inflammatory potential. • The type of the FAs on the HT core appears to be critical for defining the bioactivity of lipophenols. • HT and HT-lipophenols modulate differentially the quantitative isoprostanoid profile. Presently, the attention given to natural substances to counteract damage produced by oxidative stress (OS) has risen sharply. In this scenario, hydroxytyrosol (HT) derivatives, formed as a result of HT conjugation with fatty acids (FAs) (lipophenols), have been recently described in foodstuffs such as extra virgin olive oil, as being powerful bioactive compounds with a higher activity than the unesterified phenolic compound. The present work describes the capacity of HT lipophenols to act on the course of OS and secondary inflammatory processes, based on their capacity to modulate the isoprostanoid profile induced by H 2 O 2 in THP-1 monocytic cells. A UHPLC-QqQ-ESI-MS/MS-based lipidomics workflow was applied over a range of 37 human oxylipins. The main outcomes retrieved suggest both HT and HT-lipophenols as regulators of the cellular redox balance, acting as pro-oxidants in vitro , which is highly dependent on the experimental conditions. Our outcomes suggest the anti-inflammatory potential of both HT and HT-lipophenols, where the type of the FAs on the HT core appears to be critical for defining the bioactivity of lipophenols, highlighting that a lipidomic approach, with the simultaneous analysis of multiple oxylipins, is critical for the understanding of the bioactivity of lipophenols on isoprostanoid generation and hence, on pathophysiological processes. [ABSTRACT FROM AUTHOR]