Pro-Atherogenic and Pro-Oxidant Diets Influence Semen and Blood Traits of Rabbit Bucks

: Many dietary factors can affect sperm traits. We compared the effect of diets rich in pro-oxidant (flaxseed oil) and pro-atherogenic (coconut oil) substances without added antioxidants on semen traits, using the rabbit as an animal model. Thirty rabbit bucks (8 months old) were fed three diets for 150 days: CNT (control) a standard diet; HA (high-atherogenic) standard diet + 3% coconut oil, and HO (high-oxidizing) standard diet + 3% flaxseed oil. Semen samples were collected weekly for the evaluation of qualitative traits (kinetics, viability) and the oxidative damage (MDA and cytokines). Blood was collected at the start (T0) and end (T8) of the experimental period for the assessment of the oxidative damage (MDA and isoprostanoids), lipid profile, and testosterone. A worsening of sperm kinetics and viability was recorded in the HA group. Lipid oxidation in seminal plasma, as well as isoprostanoids in blood (F3-IsoPs and F4-NeuroPs), increased in both the HO and HA groups. A high level of TNF-α, a marker of inflammatory status, was recorded in the seminal plasma of the HA group. The resulting outcomes were mainly attributable to the different fatty acid profiles (SFA vs. PUFA) of the diets, which modulated an inflammatory/oxidative response

Lipidomic approach in young adult triathletes: effect of supplementation with a polyphenols-rich juice on neuroprostane and F2-dihomo-isoprostane markers

The aim of the this study was to determine the effect of a polyphenols-rich juice (aronia-citrus juice, ACJ) on F4-neuroprostanes and F2-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-F4t-neuroprostane and 10-F4t-neuroprostane), was observed when compared with placebo stage values. Regarding the F2-dihomo-isoprostanes, a significant decrease of the neuromotor system damage biomarkers (17-F2t-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-F2t-dihomo-IsoP, suggesting a possible role in adaptation post-training. On the other hand, the changes in the excretion of 17-epi-17-F2t-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 study was supported by the project AGL2011-23690 (CICYT) (Spanish Ministry of Economy and Competitiveness). This work has been partially funded by the “Fundación Séneca de la Región de Murcia” Grupo de Excelencia 19900/GERM/15. LAGF was granted a pre-doctoral FPI fellowship (BES2012-060185) by the Spanish government

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 pathophysio-logical factors in cardiovascular events. The targeted modulation of the endogenous mechanisms of inflamma-tion, 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 inter-vention and a reduction in hospitalizations

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 β-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

Assessment oxidative stress biomarkers –neuroprostanes and dihomo-isoprostanes- in elite triathletes urine after two weeks of moderate altitude training

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 and four F2-dihomo-isoprostanes quantified in 24-hour 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 (n=8) and a group submitted to Sea Level Training (n=8), with a Control group of non-athletes (n=8). After experimental period, the Altitude Training 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 control group and sea level training groups, no significant changes had occurred at the end of the 2-weeks 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 (CNS) compared to similar training at sea level.This study was supported by the project AGL2011-23690 (CICYT) (Spanish Ministry of Economy and Competitiveness). LAGF was granted with a pre-doctoral FPI fellowship BES2012-060185 by the Spanish government. The authors are also grateful to the University of Alicante for its collaboration. Sonia Medina was appointed under a research contract from the project AGL2011-23690 (CICYT)

Polymeric nanocapsules prevent oxidation of core-loaded molecules: evidence based on the effects of docosahexaenoic acid and neuroprostane on breast cancer cells proliferation

International audienceBackground:Nanocapsules, as a delivery system, are able to target drugs and other biologically sensitive moleculesto specific cells or organs. This system has been intensively investigated as a way to protect bioactives drugs frominactivation upon interaction with the body and to ensure the release to the target. However, the mechanism ofimproved activity of the nanoencapsulated molecules is far from being understood at the cellular and subcellularlevels. Epidemiological studies suggest that dietary polyunsaturated fatty acids (PUFA) can reduce the morbidityand mortality from breast cancer. This influence could be modulated by the oxidative status of the diet and it hasbeen suggested that the anti-proliferative properties of docosahexaenoic acid (DHA) are enhanced by pro-oxidantagents Methods:The effect of encapsulation of PUFA on breast cancer cell proliferation in different oxidative mediumwas evaluated in vitro. We compared the proliferation of the human breast cancer cell line MDA-MB-231 and ofthe non-cancer human mammary epithelial cell line MCF-10A in different experimental conditions. Results:DHA possessed anti-proliferative properties that were prevented by alpha-tocopherol (an antioxidant) andenhanced by the pro-oxidant hydrogen peroxide that confirmsthat DHA has to be oxidized to exert its anti-proliferativeproperties. We also evaluated the anti-proliferative effects of the 4(RS)-4-F4t-neuroprostane, a bioactive, non-enzymaticoxygenated metabolite of DHA known to play a major role inthe prevention of cardiovascular diseases. DHA-loadednanocapsules was less potent than non-encapsulated DHA while co-encapsulation of DHA with H2O2maintainedthe inhibition of proliferation. The nanocapsules slightly improves the anti-proliferative effect in the case of4(RS)-4-F4t-neuroprostane that is more hydrophilic than DHA. Conclusion:Overall, our findings suggest that the sensitivity of tumor cell lines to DHA involves oxidized metabolites.They also indicate that neuroprostane is a metabolite participating in the growth reducing effect of DHA, but it is not thesole. These results also suggest that NC seek to enhance the stability against degradation, enhance cellular availability,and control the release of bioactive fatty acids following their lipophilicities

Dietary antioxidant intake is inversely associated with 2,3-dinor oxylipin metabolites, the major excreted oxylipins in overweight and obese subjects

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) and 15-F-IsoPs (2,3-dinor-15-F-IsoP and 2,3-dinor-15-epi-15-F-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.The authors thank the volunteers who agreed to participate in this study, the Colombian Ministry of science, technology, and innovation (Minciencias; grant number 832-2018), and Grupo Empresarial Nutresa. They also thank the Ibero-American Programme for Science, Technology and Development (CYTED) – Action 112RT0460 CORNUCOPIA networ

Isoprostanoids quantitative profiling of marine red and brown macroalgae

International audienc