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Enzymatically formed oxygenated metabolites of polyunsaturated fatty acids (PUFA) are of great interest for the scientific community being mediators and biomarkers in the physiological and pathological regulation of many key biological processes. More recently; metabolites of PUFA formed through a non-enzymatic free radical pathway have gained interest in diseases linked with oxidative stress. Thus, synthetic strategies leading to the total synthesis of such metabolites are an essential field of research, and this review will cover a structural presentation, will discuss their biological interests, and present total syntheses reported between 2008 and 2017.1 Introduction2 Non-Enzymatic Metabolites of PUFAs2.1 Where Do They Come From?2.2 Why Are They Interesting Metabolites?2.3 A Huge Family of Natural Compounds2.3.1 Presentation of All Families2.3.1.1 Isoprostanoids2.3.1.2 Isofuranoids2.3.1.3 Isoketals2.3.2 Nomenclature of These Metabolites2.3.2.1 Isoprostanoids2.3.2.2 Isofuranoids2.3.2.3 Isoketals3 Total Synthesis Strategies3.1 Isoprostanoids3.2 Isofuranoids3.3 Isoketals4 The Discoveries Behind the Synthesis4.1 Recent Identification and Biomarkers Roles of Isoprostanes and Isofuranes4.2 Biological Properties4.2.1 Phytoprostanes, Isoprostanes, and Neuroprostanes4.2.2 Epoxy-isoprostanes5 Conclusion

International audience; Introduction: Alzheimer Disease (AD) standard diagnosis is based on evaluations and biomarkers that are non-specific, expensive, or requires invasive sampling. Therefore, an early, and non-invasive diagnosis is required. As regards molecular mechanisms, recent research has shown that lipid peroxidation plays an important role.Methods: Well-defined participants groups were recruited. Lipid peroxidation compounds were determined in plasma using a validated analytical method. Statistical studies consisted of an elastic-net-penalized logistic regression adjustment.Results: The regression model fitted to the data included six variables (lipid peroxidation biomarkers) as potential predictors of early AD. This model achieved an apparent area under the receiver operating characteristics (AUC-ROCs) of 0.883 and a bootstrap-validated AUC-ROC of 0.817. Calibration of the model showed very low deviations from real probabilities.Conclusion: A satisfactory early diagnostic model has been obtained from plasma levels of 6 lipid peroxidation compounds, indicating the individual probability of suffering from early AD.

Docosahexaenoic acid (DHA), an abundant fatty acid in the brain, is susceptible to auto-oxidation in situ and releases metabolites such as F

Photochemical and oxidative damages in retinal pigment epithelial (RPE) cells are key events in the pathogenesis of age-related macular degeneration. Polyunsaturated fatty acids (PUFA) and carotenoids are rich in retinal cells, and under oxidative stress leads to oxidation and release lipid mediators. We evaluated the impact of carotenoids (lutein, zeaxanthin) and docosahexaenoic acid (DHA) supplementation on RPE cells under oxidative stress. ARPE-19 cells were exposed to H

Background Acute kidney injury (AKI) is an important complication after major surgery and solid organ transplantation. Here, we present a dietary omega-3 polyunsaturated fatty acid (n3-PUFA) supplementation study to investigate whether pre-treatment can reduce ischemia induced AKI in mice. Methods Male 12–14 week old C57BL/6 J mice received a linoleic acid rich sunflower oil based standard diet containing 10 % fat (STD) or the same diet enriched with n3-PUFA (containing 1 % EPA and 1 % DHA) (STD + n3). After 14 days of feeding bilateral 30 min renal ischemia reperfusion injury (IRI) was conducted to induce AKI and mice were sacrificed at 24 h. Serum creatinine and blood urea nitrogen (BUN) as well as liver enzyme elevation were measured. Kidney damage was analyzed by histology and immunohistochemistry. Furthermore, pro-inflammatory cytokines (IL-6, MCP-1) were determined by qPCR. FA and oxylipin pattern were quantified in blood and kidneys by GC-FID and LC–MS/MS, respectively. Results n3-PUFA supplementation prior to renal IRI increased systemic and renal levels of n3-PUFA. Consistently, eicosanoids and other oxylipins derived from n3-PUFA including precursors of specialized pro-resolving mediators were elevated while n6-PUFA derived mediators such as pro-inflammatory prostaglandins were decreased. Feeding of n3-PUFA did not attenuate renal function impairment, morphological renal damage and inflammation characterized by IL-6 and MCP-1 elevation or neutrophil infiltration. However, the tubular transport marker alpha-1 microglobulin (A1M) was significantly higher expressed in proximal tubular epithelial cells of STD + n3 compared to STD fed mice. This indicates a better integrity of proximal tubular epithelial cells and thus significant protection of tubular function. In addition, heme oxygenase-1 (HO-1) which protects tubular function was also up-regulated in the treatment group receiving n3-PUFA supplemented chow. Discussion We showed that n3-PUFA pre-treatment did not affect overall renal function or renal inflammation in a mouse model of moderate ischemia induced AKI, but tubular transport was improved. In conclusion, dietary n3-PUFA supplementation altered the oxylipin levels significantly but did not protect from renal function deterioration or attenuate ischemia induced renal inflammation.

Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are prostaglandin-like compounds, contributing to defense signaling and prevention of cellular damage. These plant oxylipins result from autoxidation of α-linolenic acid (ALA) and have been proposed as new bioactive compounds due to their structural analogies with isoprostanes (IsoPs) and prostanoids derived from arachidonic acid in mammals, which have demonstrated diverse biological activities. The present work assesses a wide range of vegetable oils - including extra virgin olive oils (n = 7) and flax, sesame, argan, safflower seed, grapeseed, and palm oils - for their content of PhytoPs and PhytoFs. Flax oil displayed the highest concentrations, being notable the presence of 9-epi-9-D1t-PhytoP, 9-D1t-PhytoP, 16-B1-PhytoP, and 9-L1-PhytoP (7.54, 28.09, 28.67, and 19.22 μg mL−1, respectively), which contributed to a total PhytoPs concentration of 119.15 μg mL−1, and of ent-16-(RS)-9-epi-ST-Δ14-10-PhytoF (21.46 μg mL−1). Palm and grapeseed oils appeared as the most appropriate negative controls, given the near absence of PhytoPs and PhytoFs (lower than 0.15 μg mL−1). These data inform on the chance to develop nutritional trials using flax and grapeseed oils as food matrices that would provide practical information to design further assays intended to determine the actual bioavailability/bioactivity in vivo.

A unified acid/base synthetic access to tartrate-based chiral ionic liquids relying on the generation of cation hydroxide salts with AgOH was challenged with the preparation of sensitive 1-ethyl-3-methylimidazolium derivatives. Systematic variation of the starting tartaric acid stoichiometry and configuration led to eight stereoisomeric 1-ethyl-3-methylimidazolium hydrogen tartrate or di-(1-ethyl-3-methylimidazolium)tartrate entities. These salts were all characterised as proper ionic liquids. An unprecedented influence of the configuration ((2S,3S), or (2R,3R) vs. racemic or meso) on dynamic viscosity was observed. The relevance of such tartrate salts as task-specific ionic liquids was demonstrated in a synthetically useful base-promoted intramolecular cyclisation of a C2-symmetrical bis-epoxide en route to the total synthesis of phytofuran metabolites.

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 &lt, 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 &lt, 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.

Background: Alzheimer disease (AD) is an increasingly common neurodegenerative disease, especially in countries with aging populations. Its diagnosis is complex and is usually carried out in advanced stages of the disease. In addition, lipids and oxidative stress have been related to AD since the earliest stages. A diagnosis in the initial or preclinical stages of the disease could help in a more effective action of the treatments. Methods: Isoprostanoid biomarkers were determined in plasma samples from preclinical AD participants (n = 12) and healthy controls (n = 31) by chromatography and mass spectrometry (UPLC-MS/MS). Participants were accurately classified according to cerebrospinal fluid (CSF) biomarkers and neuropsychological examination. Results: Isoprostanoid levels did not show differences between groups. However, some of them correlated with CSF biomarkers (t-tau, p-tau) and with cognitive decline. In addition, a panel including 10 biomarkers showed an area under curve (AUC) of 0.96 (0.903–1) and a validation AUC of 0.90 in preclinical AD prediction. Conclusions: Plasma isoprostanoids could be useful biomarkers in preclinical diagnosis for AD. However, these results would require a further validation with an external cohort.

At present, people with today's busy lifestyle have a general trend of consuming fruit like banana passion fruit (Passiflora tripartita var. mollisima) as juices or smoothies, being an increasing tendency that can generate a large amount of agro-industrial residues. Whereby, food industries have a significant investment to minimize these wastes generated or devise alternatives of residue use. So, food researches are aimed to exploit these fruit waste. In this sense, this study has allowed the detection for the first time, in banana passion fruit shell, phytoprostanes (PhytoPs), oxylipins with multiple biological activities in humans. Furthermore, this study, with methodology used (LC-MS) allowed us to detect higher amount of these compounds (2318.63 ± 71.51 µg/100 g DW) than other vegetable matrices previously studied (macroalgae, olives or almonds, among others). In addition, we were able to identify 14 phenolic compounds (including cinnamoyl acid derivatives, flavonoid-O-glycoside, flavonoid-C-glycosides), not previously described in this matrix. Hence, this work increased the knowledge about the bioactive compounds profile of banana passion fruit shells and thereby to achieve a product with added value that may be used as natural source of bioactive compounds as alternative of synthetic substances in several industries of pharmaceutic or cosmetic fields.

The genus Passiflora , comprising about 500 species, is the largest in the Passion flower family. Passiflora edulis Sims f. edulis (gulupa) is one of the most important fruits cultivated in Colombia. In recent years and due to its organoleptic and bioactive properties, its exports have significantly increased. In this work, six new bioactive oxylipins –phytoprostanes – were detected in gulupa shell by a UHPLC-QqQ-MS/MS method: F 1t -phytoprostanes and D 1t -phytoprostanes were the predominant and minor classes, respectively. Moreover, the polyphenol profile of the shell was investigated and we were able to detect and quantify phenolic compounds that have not been described previously, like luteolin-8- C -(2- O -rhamnosyl)hexoside and quercetin-3- O -(6″-acetyl)glucosyl-2″-sinapic acid. Consequently, this study provides new insights into the importance of gulupa shell as a valuable option in the design of new beverages rich in antioxidant phytochemicals, as part of a well-balanced diet, and in the process and quality control of such products.

International audience; F4-neuroprostanes, F3-neuroprostanes n-6 DPA , and F2-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-F2t-isoprostane (also known as 8-iso-PGF 2α) , a F2-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-F3t-NeuroP n-6 DPA , ent−7(RS)−7-F2t-dihomo-IsoP, and ent−7(S)−7-F2t-dihomo-IsoP) and in our reference oxidative marker (15-F2t-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.

The goal of this work was the identification and quantification of phytoprostanes (PhytoPs) in three types of nuts: "Walnut", "Macadamia", and "Pecan". This study represents a first approach to the relationship between the quantitative and qualitative PhytoP profiles in the "Macadamia" and "Pecan" nuts subjected to fried salt or fried honey processing. The kernels were found to contain 9-F

International audience; The deuteration of polyunsaturated fatty acids (PUFAs) at their bis-allylic positions is known to limit harmful lipid peroxidation, which leads to the damage of cell membranes. Therefore, to impede toxic lipid peroxidation in retina tissue, we have designed and synthesized two deuterated analogues of docosahexaenoic acid (DHA; C22:6, n-3), which is the main lipid constituent of retina membranes. To avoid its oxidative degradation into toxic carboxyethylpyrrole (CEP) adducts, whilst preserving enzymatic metabolization into a healthy neuroprotectine derivative (NPD1), deuterium was incorporated at specific 6- and 6,9-bis-allylic positions. A convergent synthetic strategy, based on a Wittig olefination, was developed to obtain both deuterated DHA species. Common aldehyde intermediates were synthesized from another PUFA, eicosapentaenoic acid (EPA; C20:5, n-3). Deuterium atoms were introduced through either the reduction of an ester with a deuterated reagent or a nucleophilic reaction with deuterated paraformaldehyde.

International audience; Adrenic acid (AdA) and docosahexaenoic acid (DHA) peroxidation produces F 2-dihomo-IsoPs and neuro-prostanes, which have been related to oxidative damage in the central nervous system. Besides poly-phenols, melatonin (MEL) and hydroxytyrosol (OHTyr) could be partly responsible for the antioxidant benefits of red wine (excluding colon derivatives). In order to elucidate whether these compounds are responsible for the protective antioxidant effects of red wine, a double-blind, crossover, placebo-controlled in vivo study-involving the intake of red wines and their native musts by healthy volunteers-was performed. The urinary metabolites decreased after the administration of red wines, to a greater extent than after the intake of their corresponding musts or ethanol. Melatonin is the most effective compound that protects adrenic acid from oxidative attack, judged by the reduction in the formation of F 2-dihomo-isoprostanes. Similarly, hydroxytyrosol, being the most effective bioactive compound in reducing the formation of F 3-neuroprostanes n-6 DPA and F 4-neuroprostanes, protected docosahexaenoic and eicosapentaenoic acids from oxidative attack.

The enantioselective total synthesis of the highly reactive isoketal 5-D2-IsoK was accomplished. The synthesis involved construction of the isoketal core by an organocatalyzed Michael addition between ideally functionalized aldehyde and nitroolefin partners with good enantioselectivity. The lateral chains were branched through Horner–Wadsworth-Emmons and Wittig olefinations to provide flexibility, whereas the final deprotection and oxidation steps were performed under mild conditions to avoid known racemization and/or degradation of the very sensitive isoketal.

Low HDL cholesterol (HDL-C) is a risk factor for coronary artery disease (CAD). However, interventions that raise HDL-C have failed to reduce cardiovascular events. We previously reported that HDL is the main carrier of plasma F2-isoprostanes (F2-IsoPs) that are markers of oxidative stress formed upon oxidation of arachidonic acid. F2-IsoPs are predominantly associated with phospholipids. However, there is evidence that F2-IsoPs in the liver of rats treated with carbon tetrachloride associate with the neutral lipids. To date it is not known whether F2-IsoPs are found in the neutral lipids in HDL in humans. Possible candidate neutral lipids include cholesteryl esters, triglycerides, diglycerides, and monoglycerides. This study aimed to identify the lipid classes within native and oxidized HDL that contain F2-IsoPs. We showed that F2-IsoPs in HDL are bound to neutral lipids as well as phospholipids. HDL-3 contained the highest concentration of F2-IsoPs in all lipid classes before and after in vitro oxidation. Using targeted LC/MS and high resolution MS, we were unable to provide conclusive evidence for the presence of the synthesized standards 15(R)-15-F2t-isoP cholesterol and 1-ent-15(RS)-15-F2t-isoprostanoyl-sn-glycerol in the neutral lipids of HDL. Our findings show that oxidized lipids such as F2-IsoPs are found in the core and surface of HDL. However, the exact molecular species remain to be definitively characterized. Future studies are required to determine whether the presence of F2-IsoPs in neutral lipids alters HDL function.

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 F1t series. The PhytoP levels increased significantly with the time of storage (3 and 6months) 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.

International audience; Pasteurized donor human milk (DHM) is the preferred alternative for infant nutrition when own mother's milk (OMM) is unavailable. Whether DHM is an efficient means for protecting preterm infants from oxidative stress remains unknown. We quantified a panel of oxidative stress biomarkers in urine samples from preterm infants (≤32 weeks of gestation and a birth weight ≤1500 g) receiving ≥80% of feeding volume as either DHM or OMM. The noninvasive in vivo assessment of oxidative stress showed no statistically significant difference between both groups at the time when full enteral nutrition (150 mL/kg body weight) was achieved and until hospital discharge. In addition, the changes of urinary biomarker levels with time were assessed. This is the first longitudinal study on oxidative stress levels in preterm infants fed with DHM in comparison with OMM. There is no statistically significant difference in urinary oxidative stress levels of preterm infants from both groups indicating that despite the effects of pasteurization, DHM is a valid alternative when OMM is not available. Based on the results, we raise the hypothesis that pasteurized DHM protects preterm infants from oxidative stress as good as OMM, and consequently, its use could prevent oxidative stress-related diseases. Antioxid. Redox Signal. 31, 791-799.

International audience; Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are isoprostanoids that result from the peroxidation of α-linolenic acid and are biomarkers of oxidative stress in plants and humans. These compounds exhibit several interesting biological activities (e.g. neuroprotection and anti-inflammatory activities). The aim of this research was to add value to coffee pulp (CP), cocoa husk (CH) and cocoa pod husk (CPH) by identifying and quantifying PhytoPs and PhytoFs by liquid chromatography–tandem mass spectrometry. The contents of PhytoPs and PhytoFs in CP, CH, and CPH were, respectively, 654.6, 474.3 and 179.9, and 543.2, 278.0 and 393.8 ng per g dry weight (dw). The main PhytoP found in CP (171.37 ng per g dw) and CPH (37.12 ng per g dw) was 9-epi-9-F1t-PhytoP, while ent-9-L1t-PhytoP was the most abundant in CH (109.78 ng per g dw). The main PhytoF found in all sources was ent-16(RS)-13-epi-ST-Δ14-9-PhytoF, at 196.56, 126.22, and 207.57 ng per g dw in CP, CH, and CPH, respectively. We provide the first complete profile of PhytoPs and PhytoFs for these agro-residues, which could be used in the functional food industry for enriching food or as nutritional supplements.

International audience; Preterm newborns have an immature antioxidant defense system and are especially susceptible to oxidative stress. Resuscitation, mechanical ventilation, intermittent hypoxia and apneic episodes require frequently oxygen supplementation which leads to oxidative stress in preterm newborns. The consequences of oxidative damage are increased short and long-term morbidities, neurodevelopmental impairment and increased mortality. Oxidative stress biomarkers are determined in blood samples from preterm children during their stay in neonatal intensive care units especially for research purposes. However, there is a tendency towards reducing invasive and painful techniques in the NICU (Neonatal Intensive Care Unit) and avoiding excessive blood extractions procedures. In this paper, it has been described some studies that employed non-invasive samples to determine oxidative stress biomarkers form preterm infants in order to perform a close monitoring biomarker with a significant greater predictive value. Among these methods we describe a previously developed and validated high-performance liquid chromatography tandem mass spectrometry method that allow to accurately determine the most reliable biomarkers in biofluids, which are non-invasively and painlessly obtained.

International audience; 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

International audience; Krabbe disease (KD) is a rare and devastating pediatric leukodystrophy caused by mutations in the galactocerebrosidase (GALC) gene. The disease leads to impaired myelin formation and extensive myelin damage in the brain. Oxidative stress is implicated in the pathogenesis of KD but insofar few information is available. The gray and white matter of the brain are rich in docosahexaenoic acid and adrenic acid respectively and under non-enzymatic oxidative stress, release isoprostanoids, i.e. F4-neuroprostanes (F4-NeuroPs) and F2-dihomo-isoprostanes (F2-dihomo-IsoPs). In this study, the formation of isoprostanoids in brain tissue was investigated in a well-established KD mouse model (twitcher) that recapitulates the human pathology. According to the genotype determinations, three groups of mice were selected: wild-type control mice (n = 13), heterozygotes mice (carriers of GALC mutations, n = 14) and homozygous twitcher mice (n = 13). Measurement of F2-dihomo-IsoP and F4-NeuroP levels were performed on whole brain tissue obtained at day 15 and day 35 of the life cycle. Brain isoprostanoid levels were significantly higher in the twitcher mice compared to the heterozygous and wild-type control mice. However, F2-dihomo-IsoP and F4-NeuroP levels did not differ in brain of day 15 compared to day 35 of the heterozygote mice. Interestingly, isoprostanoid levels were proportionally enhanced with disease severity (F2-dihomo-IsoPs, rho = 0.54; F4-NeuroPs, rho = 0.581; P values ≤ 0.05; n = 13). Our findings are the first to show the key role of polyunsaturated fatty acid oxidative damage to brain grey and white matter in the pathogenesis and progression of KD. This shed new insights on the biochemical indexes of KD progression, and potentially provide information for novel therapeutic targets.

Consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) rich fatty fish is known to provide an array of health benefits. However, high temperature in food preparation, such as pan-frying, potentially degrades eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of the n-3 PUFAs by heat oxidation. The addition of antioxidant condiments, and herbs in particular, may retard PUFA peroxidation and preserve EPA and DHA during pan-frying. In this study, different types of antioxidant condiments (sage, rosemary, black peppercorn, thyme, basil, and garlic) were tested for antioxidant capacity, and the condiment with the highest capacity was selected for its effect on lipid oxidation of salmon. The changes in fatty acids and lipid peroxidation of salmon, during pan-frying with the selected condiment (olive oil infused with rosemary, RO(infused)), were compared with salmon prepared in extra virgin olive oil, olive oil, or without oil. The total saturated fatty acid was found to be less in pan fried salmon with RO(infused). None of the oil type conserved EPA- and DHA-content in salmon. However, RO(infused) lowered lipid peroxidation by lessening hydroperoxide and 4-HNE formation, but not the other related products (HDHA, HETE, isoprostanes). Our observation indicates that the antioxidant capacity of RO(infused), when it is incorporated with food, becomes limited.

International audience; The cardioprotective and anti-inflammatory effects of long chain omega-3 polyunsaturated fatty acids (n3 PUFA) are believed to be partly mediated by their oxygenated metabolites (oxylipins). In the last two decades interest in a novel group of autacoids termed specialized pro-resolving mediators (SPMs) increased. These are actively involved in the resolution of inflammation. SPMs are multiple hydroxylated fatty acids including resolvins, maresins, and protectins derived from the n3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as well as lipoxins derived from arachidonic acid (ARA). In the present paper, we developed an LC-MS/MS method for a comprehensive set of 18 SPMs derived from ARA, EPA, and DHA and integrated it into our targeted metabolomics platform. Quantification was based on external calibration utilizing five deuterated internal standards in combination with a second internal standard for quality assessment of sample preparation in each sample. The tandem mass spectrometric parameters were carefully optimized for sensitive and specific detection. The influence of source parameters of the used AB Sciex 6500 QTRAP instrument as well as electronic parameters and the selection of transitions are discussed. The method was validated/characterized based on the criteria listed in the European Medicines Agency (EMA) guideline on bioanalytical method validation and method performance is demonstrated regarding recovery of internal standards (between 78 ± 4% and 87 ± 3% from 500 µL of human serum) as well as extraction efficacy of SPMs in spiked plasma (intra-day accuracy within ±20 and ±15% at 0.1 and 0.3 nM in plasma, respectively). Based on the lower limit of quantification of 0.02-0.2 nM, corresponding to 0.18-2.7 pg on column, SPMs were generally not detectable/quantifiable in plasma and serum supporting that circulating levels of SPMs are very low, i.e.

Despite recent advances in our understanding of the biological processes leading to the development and progression of cancer, there is still a need for new and effective agents to treat this disease. Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are non-enzymatically oxidized products of &alpha, linolenic acid that are present in seeds and vegetable oils. They have been shown to possess anti-inflammatory and apoptosis-promoting activities in macrophages and leukemia cells, respectively. In this work, seven PhytoPs (PP1&ndash, PP7) and one PhytoFs (PF1) were evaluated for their cytotoxic, chemosensitization, and anti-migratory activities using the MCF-7 and MDA-MB-231 breast cancer cell lines. Among the tested compounds, only three PhytoPs had a significant effect on cell viability compared to the control group: Ent-9-L1-PhytoP (PP6) decreased cell viability in both cell lines, while 16-F1t-PhytoP (PP1) and 9-L1-PhytoP (PP5) decreased viability of MCF-7 and MDA-MB-231 cells, respectively. When combined with a sub-cytotoxic dose of doxorubicin, these three PhytoPs displayed significantly enhanced cytotoxic effects on MCF-7 cells while the chemotherapeutic drug alone had no effect. In cellular motility assays, Ent-9-(RS)-12-epi-ST-&Delta, 10-13-PhytoF could significantly inhibit cellular migration of MDA-MB-231 cells. In addition, Ent-9-(RS)-12-epi-ST-&Delta, 10-13-PhytoF also enhanced cellular adhesion of MDA-MB-231 cells.

Alzheimer Disease (AD) standard biological diagnosis is based on expensive or invasive procedures. Recent research has focused on some molecular mechanisms involved since early AD stages, such as lipid peroxidation. Therefore, a non-invasive screening approach based on new lipid peroxidation compounds determination would be very useful. Well-defined early AD patients and healthy participants were recruited. Lipid peroxidation compounds were determined in urine using a validated analytical method based on liquid chromatography coupled to tandem mass spectrometry. Statistical studies consisted of the evaluation of two different linear (Elastic Net) and non-linear (Random Forest) regression models to discriminate between groups of participants. The regression models fitted to the data from some lipid peroxidation biomarkers (isoprostanes, neuroprostanes, prostaglandines, dihomo-isoprostanes) in urine as potential predictors of early AD. These prediction models achieved fair validated area under the receiver operating characteristics (AUC-ROCs > 0.68) and their results corroborated each other since they are based on different analytical principles. A satisfactory early screening approach, using two complementary regression models, has been obtained from urine levels of some lipid peroxidation compounds, indicating the individual probability of suffering from early AD.

In rice crops, fertilization is a naturalized practice, although inefficient, that could be improved by applying foliar fertilization. Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are products of α-linolenic acid peroxidation, useful as biomarkers of oxidative degradation in higher plants. The objective was to determine the effect of the foliar fertilization on the concentration of PhytoPs and PhytoFs and its relationships with modifications of yield and quality of rice productions. It was described that the concentration of biomarkers of stress decreased with the application of foliar fertilization, being the response significantly different depending the genotypes and compound monitored. Moreover, fertilization did not modify significantly the parameters of yield (961.2 g m−2), 1000 whole-grain (21.2 g), and protein content (10.7% dry matter). Therefore, this is the first work that describes the effect of fertilization on PhytoPs and PhytoFs in rice genotypes and reinforces the capacity of these compounds as biomarkers to monitor specific abiotic stress, in this case, represented by nutritional stress., Facultad de Ciencias Agrarias y Forestales

Oxidative stress plays a crucial role in developing and accelerating retinal diseases including age-related macular degeneration (AMD). Docosahexaenoic acid (DHA, C22:6, n-3), the main lipid constituent of retinal epithelial cell membranes, is highly prone to radical and enzymatic oxidation leading to deleterious or beneficial metabolites for retinal tissue. To inhibit radical oxidation while preserving enzymatic metabolism, deuterium was incorporated at specific positions of DHA, resulting in D2-DHA when incorporated at position 6 and D4-DHA when incorporated at the 6,9 bis-allylic positions. Both derivatives were able to decrease DHAs&rsquo, toxicity and free radical processes involved in lipid peroxidation, in ARPE-19 cells (Adult Retinal Pigment Epithelial cell line), under pro-oxidant conditions. Our positive results encouraged us to prepare lipophenolic-deuterated-DHA conjugates as possible drug candidates for AMD treatment. These novel derivatives proved efficient in limiting lipid peroxidation in ARPE-19 cells. Finally, we evaluated the underlying mechanisms and the enzymatic conversion of both deuterated DHA. While radical abstraction was affected at the deuterium incorporation sites, enzymatic conversion by the lipoxygenase 15s-LOX was not impacted. Our results suggest that site-specifically deuterated DHA could be used in the development of DHA conjugates for treatment of oxidative stress driven diseases, or as biological tools to study the roles, activities and mechanisms of DHA metabolites.

International audience; A set of 19 oxadiazolone (OX) derivatives have been investigated for their antimycobacterial activity against two pathogenic slow-growing mycobacteria, Mycobacterium marinum and Mycobacterium bovis BCG, and the avirulent Mycobacterium tuberculosis (M. tb) mc26230. The encouraging minimal inhibitory concentrations (MIC) values obtained prompted us to test them against virulent M. tb H37Rv growth either in broth medium or inside macrophages. The OX compounds displayed a diversity of action and were found to act either on extracellular M.tb growth only with moderated MIC50, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth. Of interest, all OX derivatives exhibited very low toxicity towards host macrophages. Among the six potential OXs identified, HPOX, a selective inhibitor of extracellular M. tb growth, was selected and further used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP, in order to identify its putative target(s). This approach, combined with mass spectrometry, identified 18 potential candidates, all being serine or cysteine enzymes involved in M. tb lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA, TesA, KasA and MetA have been reported as essential for in vitro growth of M. tb and/or its survival and persistence inside macrophages. Overall, our findings support the assumption that OX derivatives may represent a novel class of multi-target inhibitors leading to the arrest of M. tb growth through a cumulative inhibition of a large number of Ser- and Cys-containing enzymes involved in various important physiological processes.

Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are oxylipins synthesized by nonenzymatic peroxidation of α-linolenic acid. These compounds are biomarkers of oxidative degradation in plant foods. In this research, the effect of environment and supplementation with salicylic acid (SA) on PhytoPs and PhytoFs was monitored by ultra-high-performance liquid chromatography coupled to electrospray ionization and triple quadrupole mass spectrometry (UHPLC-ESI-QqQ-MS/MS) on seven rice genotypes from Oryza sativa L. subsp. japonica. The plastic cover environment and spray application with 1 and 15 mM SA produced a reduction in the concentration of most of these newly established stress biomarkers [9-F1t-PhytoP, ent-16-F1t-PhytoP, ent-16- epi-16-F1t-PhytoP, 9-D1t-PhytoP, 9- epi-9-D1t-PhytoP, 16-B1-PhytoP, 9-L1-PhytoP, ent-16( RS)-9- epi-ST-Δ14-10-PhytoF, ent-9( RS)-12- epi-ST-Δ10-13-PhytoF, and ent-16( RS)-13- epi-ST-Δ14-9-PhytoF] by 60.7% on average. The modification observed in the level of PhytoPs and PhytoFs differed according to the specific oxylipins and genotype, demonstrating a close linkage between genetic features and resistance to abiotic stress, to some extent mediated by the sensitivity of plants to the plant hormone SA that participates in the physiological response of higher plants to stress. Thus, in plants exposed to stressing factors, SA contribute to modulating the redox balance, minimizing the oxidation of fatty acids and thus the syntheis of oxylipins. These results indicated that SA could be a promising tool for managing the thermotolerance of rice crop. However, it remains necessary to study the mechanism of action of PhytoPs and PhytoFs in biochemical processes related to the defense of plants and define their role as stress biomarkers through a nonenzymatic pathway., Facultad de Ciencias Agrarias y Forestales

International audience; The ecological success of diatoms requires a remarkable ability to survive many types of stress, including variations in temperature, light, salinity, and nutrient availability. On exposure to these stresses, diatoms exhibit common responses, including growth arrest, impairment of photosynthesis, production of reactive oxygen species, and accumulation of triacylglycerol (TAG). We studied the production of cyclopentane oxylipins derived from fatty acids in the diatom Phaeodactylum tricornutum in response to oxidative stress. P. tricornutum lacks the enzymatic pathway for producing cyclopentane-oxylipins, such as jasmonate, prostaglandins, or thromboxanes. In cells subjected to increasing doses of hydrogen peroxide (H2O2), we detected nonenzymatic production of isoprostanoids, including six phytoprostanes, three F2t-isoprostanes, two F3t-isoprostanes, and three F4t-neuroprostanes, by radical peroxidation of α-linolenic, arachidonic, eicosapentaenoic, and docosahexanoic acids, respectively. H2O2 also triggered photosynthesis impairment and TAG accumulation. F1t-phytoprostanes constitute the major class detected (300 pmol per 1 million cells; intracellular concentration, ∼4 µm). Only two glycerolipids, phosphatidylcholine and diacylglycerylhydroxymethyl-trimethyl-alanine, could provide all substrates for these isoprostanoids. Treatment of P. tricornutum with nine synthetic isoprostanoids produced an effect in the micromolar range, marked by the accumulation of TAG and reduced growth, without affecting photosynthesis. Therefore, the emission of H2O2 and free radicals upon exposure to stresses can lead to glycerolipid peroxidation and nonenzymatic synthesis of isoprostanoids, inhibiting growth and contributing to the induction of TAG accumulation via unknown processes. This characterization of nonenzymatic oxylipins in P. tricornutum opens a field of research on the study of processes controlled by isoprostanoid signaling in various physiological and environmental contexts in diatoms.

Neuroprostanes, a family of non-enzymatic metabolites of the docosahexaenoic acid, have been suggested as potential biomarkers for neurological diseases. Objective biological markers are strongly needed in Rett syndrome (RTT), which is a progressive X-linked neurodevelopmental disorder that is mainly caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene with a predominant multisystemic phenotype. The aim of the study is to assess a possible association between MECP2 mutations or RTT disease progression and plasma levels of 4(RS)-4-F4t-neuroprostane (4-F4t-NeuroP) and 10(RS)-10-F4t-neuroprostane (10-F4t-NeuroP) in typical RTT patients with proven MECP2 gene mutation. Clinical severity and disease progression were assessed using the Rett clinical severity scale (RCSS) in n = 77 RTT patients. The 4-F4t-NeuroP and 10-F4t-NeuroP molecules were totally synthesized and used to identify the contents of the plasma of the patients. Neuroprostane levels were related to MECP2 mutation category (i.e., early truncating, gene deletion, late truncating, and missense), specific hotspot mutations (i.e., R106W, R133C, R168X, R255X, R270X, R294X, R306C, and T158M), and disease stage (II through IV). Circulating 4-F4t-NeuroP and 10-F4t-NeuroP were significantly related to (i) the type of MECP2 mutations where higher levels were associated to gene deletions (p ≤ 0.001), (ii) severity of common hotspot MECP2 mutation (large deletions, R168X, R255X, and R270X), (iii) disease stage, where higher concentrations were observed at stage II (p ≤ 0.002), and (iv) deficiency in walking (p ≤ 0.0003). This study indicates the biological significance of 4-F4t-NeuroP and 10-F4t-NeuroP as promising molecules to mark the disease progression and potentially gauge genotype–phenotype associations in RTT.

International audience; Oxygenated lipid mediators released from non-enzymatic peroxidation of polyunsaturated fatty acids (PUFA) are known to have functional roles in humans. Notably, among these lipid mediators, isoprostanes molecules are robust biomarkers of oxidative stress but those from n-3 PUFA are also bioactive molecules. In order to identify and assess the isoprostanes, the use of mass spectrometry (MS) for analysis is preferable and has been used for over two decades. Gas chromatography (GC) is commonly coupled to the MS to separate the derivatized isoprostanes of interest in biological samples. In order to increase the accuracy of the analytical performance, GC-MS/MS was also applied. Lately, MS or MS/MS has been coupled with high-performance liquid chromatography to assess multiple isoprostane molecules in a single biological sample without derivatization process. However, there are limitations for the use of LC-MS/MS in the measurement of plasma isoprostanes, which will be discussed in this review.

International audience

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.

International audience; Non-enzymatic oxygenated metabolites derived from polyunsaturated fatty acids (PUFA) are formed in vivo through free radical reaction under oxidative stress conditions. It has been over twenty-five years since the discovery of cyclic oxygenated metabolites derived from arachidonic acid (20:4 n-6), the isoprostanes, and since then they have become biomarkers of choice for assessing in vivo OS in humans and animals. Chemical synthesis of n-3 PUFA isoprostanoids such as F3-Isoprostanes from eicosapentaenoic acid (20:5 n-3), and F4-Neuroprostanes from docosahexaenoic acid (22:6 n-6) unravelled novel and unexpected biological properties of such omega-3 non-enzymatic cyclic metabolites as highlighted in this review.

International audience; Metabolites of the non-enzymatic lipid peroxidation of polyunsaturated fatty acids (DHA, n-6DPA, and AdA), neuroprostanes (NeuroPs), and F 2-dihomo-isoprostanes (F 2-dihomo-IsoPs) have become important biomarkers for oxidative stress (OS) in neurodegenerative diseases, particularly in epilepsy. These biomarkers were measured by UHPLC-QqQ-MS/MS in the urine of 30 epileptic patients treated with different antiepileptic drugs (AEDs) (old treatment (n ¼ 15) or new-generation treatments (n ¼ 15)), in comparison with 15 healthy controls. After treatment with new-generation AEDs (levetiracetam, eslicarbazepine acetate, lacosamide, and zonisamide) a decrease was observed in the total urinary neuronal membrane degradation markers (NeuroPs) and neuromotor system degradation markers (F 2-Dihomo-IsoPs), in comparison with the old treatment (carbamazepine, phenytoin, valproic acid) and control (no pharmacological treatment) groups. These results suggest that new-generation AEDs reduce the total NeuroPs/F 2-Dihomo-IsoPs to levels similar to those of the control group and hence play an important role in antioxidant systems in epileptic patients. Unfortunately, little is known currently about the neuroprotective effect of second-and third-generation AEDs; so, more clinical studies need to be performed to clarify the relationships among chronic treatment with newer AEDs, oxidative stress, and epilepsy.

International audience; Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are plant oxylipins (isoprostane-prostaglandin-like compounds) formed by the free radical-catalyzed oxidation of α-linolenic acid (ALA, C18:3, n-3). These oxylipins have been previously described in an array of plant-based foods with similar concentrations as phenolics in some fruits and vegetables, but their occurrence in dark chocolate has not been addressed so far, neither their content nor the influence of cocoa percent and fatty acid composition on the generation of PhytoPs and PhytoFs, to establish new assays in order to boost the dietary burden of these new bioactive compounds, provided by natural plant-based foods intake. In this regard, 80 dark chocolate samples with cocoa (Theobroma cacao L.) content of up to 100% were assessed on their PhytoP and PhytoF profile. These target analytes were isolated using a dispersive liquid–liquid extraction followed by a solid-phase clean-up of the extracts, and quantified using a UHPLC coupled to a triple quadrupole-MS/MS detection system. The content of PhytoPs and PhytoFs in the array of chocolates analyzed oscillated from 2.45 to 1192.43 ng/g fw and from 144.57 to 840.19 ng/g fw, respectively. The profile of these metabolites was studied in conjunction with the fatty acid methyl esters (FAMEs) content and the percentage of cocoa; however, no relationship between PhytoPs and PhytoFs and FAMEs content nor the cocoa percentage was observed. The assessment of dark chocolates on the content of PhytoPs and PhytoFs is of great importance as there is increasing scientific evidence on their immunomodulatory and inflammatory activity, as well as their role as preventive agents against oxidative stress that could confer this food an additional interest to consumers.

International audience; Biomarkers of oxidative stress are generally measured in blood and its derivatives. However, the invasiveness of blood collection makes the monitoring of such chemicals during exercise not feasible. Saliva analysis is an interesting approach in sport medicine because the collection procedure is easy-to-use and does not require specially-trained personnel. These features guarantee the collection of multiple samples from the same subject in a short span of time, thus allowing the monitoring of the subject before, during and after physical tests, training or competitions. The aim of this work was to evaluate the possibility of following the changes in the concentration of some oxidative stress markers in saliva samples taken over time by athletes under exercise. To this purpose, ketones (i.e. acetone, 2-butanone and 2-pentanone), aldehydes (i.e. propanal, butanal, and hexanal), α,β-unsaturated aldehydes (i.e. acrolein and methacrolein) and di-carbonyls (i.e. glyoxal and methylglyoxal) were derivatized with 2,4-dinitrophenylhydrazine, and determined by ultra-high performance liquid chromatography coupled to diode array detector. Prostaglandin E2, F2/E2-isoprostanes, F2-dihomo-isoprostanes, F4-neuroprostanes, and F2-dihomo-isofuranes were also determined by a reliable analytical procedure that combines micro-extraction by packed sorbent and ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry. Overall the validation process showed that the methods have limits of detection in the range of units of ppb for carbonyls and tens to hundreds of ppt for isoprostanes and prostanoids, very good quantitative recoveries (90–110%) and intra- and inter-day precision lower than 15%. The proof of applicability of the proposed analytical approach was investigated by monitoring the selected markers of oxidative stress in ten swimmers performing a VO2max cycle ergo meter test. The results highlighted a clear increase of salivary by-products of oxidative stress during exercise, whereas a sharp decrease, approaching baseline values, of these compounds was observed in the recovery phase. This study opens up a new approach in the evaluation of oxidative stress and its relation to aerobic activity.

The ecological success of diatoms requires a remarkable ability to survive many types of stress, including variations in temperature, light, salinity, and nutrient availability. On exposure to these stresses, diatoms exhibit common responses, including growth arrest, impairment of photosynthesis, production of reactive oxygen species, and accumulation of triacylglycerol (TAG). We studied the production of cyclopentane oxylipins derived from fatty acids in the diatom Phaeodactylum tricornutum in response to oxidative stress. P. tricornutum lacks the enzymatic pathway for producing cyclopentane-oxylipins, such as jasmonate, prostaglandins, or thromboxanes. In cells subjected to increasing doses of hydrogen peroxide (H(2)O(2)), we detected nonenzymatic production of isoprostanoids, including six phytoprostanes, three F(2t)-isoprostanes, two F(3t)-isoprostanes, and three F(4t)-neuroprostanes, by radical peroxidation of α-linolenic, arachidonic, eicosapentaenoic, and docosahexanoic acids, respectively. H(2)O(2) also triggered photosynthesis impairment and TAG accumulation. F(1t)-phytoprostanes constitute the major class detected (300 pmol per 1 million cells; intracellular concentration, ∼4 µm). Only two glycerolipids, phosphatidylcholine and diacylglycerylhydroxymethyl-trimethyl-alanine, could provide all substrates for these isoprostanoids. Treatment of P. tricornutum with nine synthetic isoprostanoids produced an effect in the micromolar range, marked by the accumulation of TAG and reduced growth, without affecting photosynthesis. Therefore, the emission of H(2)O(2) and free radicals upon exposure to stresses can lead to glycerolipid peroxidation and nonenzymatic synthesis of isoprostanoids, inhibiting growth and contributing to the induction of TAG accumulation via unknown processes. This characterization of nonenzymatic oxylipins in P. tricornutum opens a field of research on the study of processes controlled by isoprostanoid signaling in various physiological and environmental contexts in diatoms.

Consumption of food containing n-3 PUFAs, namely EPA and DHA, are known to benefit health and protect against chronic diseases. Both are richly found in marine-based food such as fatty fish and seafood that are commonly cooked prior to consumption. However, the elevated temperature during cooking potentially degrades the EPA and DHA through oxidation. To understand the changes during different cooking methods, lipid profiles of raw, boiled, pan-fried and baked salmon were determined by LC-MS/MS. Our results showed that pan-frying and baking elevated the concentration of peroxides in salmon, whereas only pan-frying increased the MDA concentration, indicating it to be the most severe procedure to cause oxidation among the cooking methods. Pan-frying augmented oxidized products of n-3 and n-6 PUFAs, while only those of n-3 PUFA were elevated in baked salmon. Notably, pan-frying and baking increased bioactive oxidized n-3 PUFA products, in particular F-4t-neuroprostanes derived from DHA. The results of this study provided a new insight into the application of heat and its effect on PUFAs and the release of its oxidized products in salmon.

International audience; Isoprostanoids are a large family of compounds derived from non-enzymatic oxidation of polyunsaturated fatty acids (PUFAs). Unlike other oxidative stress biomarkers, they provide unique information on the precursor of the targeted PUFA. Although they were discovered about a quarter of century ago, the knowledge on the role of key isoprostanoids in the pathogenesis of experimental and human disease models remains limited. This is mainly due to the limited availability of highly purified molecules to be used as a reference standard in the identification of biological samples. The accurate knowledge on their biological relevance is the critical step that could be translated from some mere technical/industrial advances into a reliable biological disease marker which is helpful in deciphering the oxidative stress puzzle related to neurological disorders. Recent research indicates the value of isoprostanoids in predicting the clinical presentation and evolution of the neurological diseases. This review focuses on the relevance of isoprostanoids as mediators and potential biomarkers in neurological diseases, a heterogeneous family ranging from rare brain diseases to major health conditions that could have worldwide socioeconomic impact in the health sector. The current challenge is to identify the preferential biochemical pathways that actually follow the oxidative reactions in the neurological diseases and the consequence of the specific isoprostanes in the underlying pathogenic mechanisms.