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As children spend up to 9 h a day in kindergarten, the main purpose of our study was to evaluate the effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers (OSBs) in healthy children. In the randomized control trial with a follow-up, healthy 5–6-year-old children from six kindergartens were randomly divided into a prototype group (PG, n = 40) and a control group (CG, n = 17). PG followed a 2-week antioxidant-rich kindergarten meal plan (breakfast, lunch, and two snacks), and CG followed their standard kindergarten meal plans. Outside the kindergartens, participants ate as usual. We used a consecutive 7-day dietary record inside and outside the kindergarten and the national dietary assessment tool OPEN to assess the total dietary antioxidant capacity (dTAC) of the consumed foods. Malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and four F2-isoprostane were measured in fasting urine on days 1 and 15. We also measured total antioxidant power (PAT) and hydroperoxides (d-ROMs) in fasting serum on day 15 and obtained the value of the oxidative stress index (OSI). We used a Welch two-sample t-test and multiple regression analysis to compare the prototype and control groups and a nonparametric Wilcoxon signed rank exact test to compare pre- and post-intervention results in urine. Antioxidant-rich kindergarten meals contributed to a significantly (p < 0.05) higher intake of dTAC in PG participants compared to standard meals in CG participants (8.6 vs. 2.8 mmol/day). We detected a negative correlation between dTAC intake and d-ROMs and between dTAC intake and OSI (r = − 0.29, p = 0.043 and r = − 0.31, p = 0.032, respectively). A significant decrease in urinary 8-iso-15-prostaglandin-F-2 alpha was detected in PG participants between days 1 and 15; however, no other intra-individual significant differences in urinary OSBs were found. Conclusion: Antioxidant-rich food in kindergarten is warranted due to its potential health-protective effect. Additionally, we present original data on the average levels of urinary and serum OSBs in healthy 5–6-year-old children. Trial registration: The study was registered at ClinicalTrials.gov, on February 5, 2020 (https://clinicaltrials.gov/ct2/show/NCT04252105). What is Known: • Kindergartens are recognized as promising environments for public health measures. • A diet rich in antioxidants can reduce OSBs and, consequently, the risk of developing NCDs. What is New: • Antioxidant-rich kindergarten diet can ensure a protective intake of dTAC in children. • Original data on serum oxidative stress biomarkers (d-ROMs, PAT, and OSI) and urinary oxidative stress biomarkers (MDA, 8-OHdG, and F2 isoprostanes) in healthy 5–6-year-old children. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the cross-sectional association between healthy dietary patterns [alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), alternative Healthy Eating Index (aHEI), and Healthy Eating Index 2015 (HEI-2015)] and urinary biomarkers of oxidative stress. Methods: Between 2003 and 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35 to 74 (non-Hispanic White, 83.7%). Data were analyzed for 844 premenopausal and 454 postmenopausal women who had urine samples analyzed for F2-isoprostanes and non-missing covariate data. Food frequency questionnaire responses were used to calculate dietary pattern scores. Concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were measured in urine samples by GC/MS for premenopausal women and LC/MS for postmenopausal women. Multivariable linear regression models were used to estimate associations between aMED, DASH, aHEI, and HEI-2015 and urinary F2-isoprostanes by menopausal status. Effect modification by sociodemographic, lifestyle, and clinical characteristics was also evaluated. Results: Among premenopausal women, the four dietary indices were inversely associated with 8-iso-PGF2α (aMED βQ4vsQ1: − 0.17, 95% CI − 0.27, − 0.08; DASH βQ4vsQ1: − 0.18, 95% CI − 0.28, − 0.08; aHEI βQ4vsQ1: − 0.20, 95% CI − 0.30, − 0.10; HEI-2015 βQ4vsQ1: − 0.19, 95% CI − 0.29, − 0.10). In contrast, inverse associations with 8-iso-PGF2α-M were found for the continuous aMED, aHEI, and HEI-2015. Associations between dietary indices and 8-iso-PGF2α were generally stronger among younger women, women with lower income, and women with higher BMI. Similar results were observed among postmenopausal women, though only the continuous DASH and aHEI models were statistically significant. Conclusion: Healthy dietary patterns were associated with lower levels of oxidative stress. [ABSTRACT FROM AUTHOR]

BACKGROUND: Childhood wheeze, asthma, and allergic rhinitis are common and likely have prenatal origins. Oxidative stress is associated with respiratory disease, but the association of oxidative stress during the prenatal period with development of respiratory and atopic disease in childhood, particularly beyond the infancy period, is unknown. This study aims to investigate associations between prenatal oxidative stress, measured by maternal urinary F2-isoprostanes, and child respiratory outcomes, including effect modification by maternal race. METHODS: We prospectively studied Black (n = 717) and White (n = 363) mother-child dyads. We measured F2-isoprostanes in 2nd-trimester urine (ng/mg-creatinine). At approximately age 4, we obtained parent report of provider-diagnosed asthma (ever), current wheeze, current asthma (diagnosis, symptoms and/or medication), and current allergic rhinitis (current defined as previous 12 months). We used multivariable logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) per interquartile range (IQR) increase in F2-isoprostane concentration, controlling for confounders. We examined modification by maternal race using interaction terms. RESULTS: The prevalence of provider-diagnosed asthma and current wheeze, asthma and allergic rhinitis was 14%, 19%, 15%, and 24%, respectively. Median (IQR) F2-isoprostane levels were 2.1 (1.6, 2.9) ng/mg-creatinine. Associations between prenatal F2-isoprostanes and provider-diagnosed asthma, current wheeze, and current asthma were modified by maternal race. Results were strongest for current wheeze (aOR [95%CI]: 1.55 [1.16, 2.06] for White; 0.98 [0.78, 1.22] for Black; p-interaction = 0.01). We observed no association between F2-isoprostanes and allergic rhinitis. CONCLUSION: Prenatal urinary F2-isoprostanes may be a marker associated with childhood wheeze/asthma in certain populations. Research is needed to understand underlying mechanisms and racial differences.

The objective of this study was to calculate an oxidative balance score (OBS) utilizing diet and lifestyle information collected from 1322 women during the second trimester of pregnancy in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study. An energy-adjusted OBS was calculated using nutrient information from a Food Frequency Questionnaire (FFQ), lifestyle measures, and plasma folate and vitamin D levels. Using the least absolute shrinkage and selection operator method, 91 food items from the FFQ were selected and they accounted for 82% of the variance in the OBS, with cruciferous vegetables, citrus fruits, fruit juice, and coffee being among the highest anti-oxidant predictors, and red meats and alcohol among the highest pro-oxidant contributors. Urinary F2-isoprostane, an objective indicator of oxidative stress, was lower with increasing OBS quintiles in a stairstep manner (p for trend = 0.0003), suggesting the possible utility of the OBS as an indicator of oxidative stress. The OBS was moderately correlated with the Healthy Eating Index (correlation coefficient = 0.6076), suggesting it provides a distinct measure of a healthy diet. In conclusion, the OBS may serve as a valid reflective indicator of urinary F2-isoprostanes and an epidemiological tool to inform intervention studies, in order to minimize oxidative stress during pregnancy.

Obesity affects over 40% of the adult population and is a major risk factor for morbidity and mortality due to cardiovascular disease. Black women have one of the highest prevalences of obesity, insulin resistance, hypertension, and cardiovascular events in the US. We previously found that free radical-mediated lipid peroxidation contributes to IL-6 production in dendritic cells leading to inflammation and hypertension. Thus, we hypothesized that F2-isoprostanes (F2-IsoPs), products and biomarkers of endogenous lipid peroxidation, contribute to increased inflammation and IL-6 production among obese Black women. We studied a total of 88 obese Black women of age 42.0 ± 9.8 years, weight 102 ± 16 kg, and body mass index (BMI) 37.68 ± 5.08. Systolic and diastolic blood pressure were 124 ± 14/76.2 ± 9.9 mmHg, heart rate was 68.31 ± 10.26 beats/min, and fasting insulin was 15.0 ± 8.7 uU/mL. Plasma F2-IsoPs were measured using gas chromatography/negative ion chemical ionization mass spectrometry (GC/NICI-MS). Plasma cytokines, including IL-6, IL-8, IL-10, IL-1β, TNF-a, and C-reactive proteins were measured using multiplex Luminex technology. Anthropometric measurements were performed using dual-energy X-ray absorptiometry. Using Pearson’s correlation analysis, we found that BMI was positively correlated with plasma F2-IsoPs, while inversely correlated with insulin sensitivity in obese Black women. Further, F2-IsoPs were positively correlated with inflammatory marker IL-6 levels while negatively correlated with anti-inflammatory marker IL-10. In addition, we found that plasma F2-IsoPs levels were significantly associated with reduced insulin sensitivity. These results suggest that F2-IsoPs may be associated with obesity-induced cardiovascular risk in Black women by increasing the production of inflammatory cytokine IL-6 and decreasing the production of anti-inflammatory IL-10.

Green tea extract (GTE) is a potential mitigator of oxidative stress, and F 2 -isoprostanes are a reliable biomarker of oxidative stress. Genetic polymorphisms in the catechol-o-methyltransferase (COMT) gene may modify tea catechin metabolism, prolonging exposure. We hypothesized that GTE supplementation would decrease plasma F 2 -isoprostanes concentrations compared with placebo and that participants with the COMT genotype polymorphisms would experience a more significant expression of this outcome. This study was a secondary analysis of the Minnesota Green Tea Trial, a randomized placebo-controlled, double-blinded trial investigating the effects of GTE in women who were generally healthy and postmenopausal. The treatment group consumed 843 mg of epigallocatechin gallate daily for 12 months versus placebo. Participants in this study had a mean age of 60 years, were predominantly White, and most had a healthy body mass index. GTE supplementation did not significantly change plasma F 2 -isoprostanes concentrations compared with placebo after 12 months (P for overall treatment =.07). There were no significant interactions between treatment and age, or body mass index, physical activity, smoking history, and alcohol intake. COMT genotype did not modify the effect of GTE supplementation on F 2 -isoprostanes concentrations in the treatment group (P =.85). Among participants in the Minnesota Green Tea Trial, consuming GTE supplements daily for 1 year did not result in a significant decrease in plasma F 2 -isoprostanes concentrations. Likewise, the COMT genotype did not modify the effect of GTE supplementation on F 2 -isoprostanes concentrations. Green tea extract (GTE) containing the antioxidant epigallocatechin gallate may reduce oxidative stress. Polymorphisms in catechol-O-methyltransferase (COMT) decrease metabolic activity, prolonging exposure and GTE activity. GTE supplementation was compared with placebo on plasma F 2 -isoprostanes concentrations with no significant difference on participants' F 2 -isoprostane levels after 12 months. This is the first study evaluating the effect of COMT genotype on F 2 -isoprostanes. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background Despite the wide use of parenteral nutrition (PN) in neonatal intensive care units (NICU), there is limited evidence regarding the optimal time to commence PN in term and late preterm infants. The recommendations from the recently published ESPGHAN/ESPEN/ESPR/CPEN and NICE guidelines are substantially different in this area, and surveys have reported variations in clinical practice. The aim of this randomised controlled trial (RCT) is to evaluate the benefits and risks of early versus late PN in term and late preterm infants. Methods/design This study is a single-centre, non-blinded RCT in the NICU of Perth Children’s Hospital, Western Australia.A total of 60 infants born ≥34 weeks of gestation who have a high likelihood of intolerance to enteral nutrition (EN) for at least 3-5 days will be randomised to early (day 1 or day 2 of admission) or late commencement (day 6 of admission) of PN after informed parental consent. In both groups, EN will be commenced as early as clinically feasible. Primary outcomes are plasma phenylalanine and plasma F2-isoprostane levels on Day 4 and Day 8 of admission. Secondary outcomes are total and individual plasma amino acid profiles, plasma and red blood cell fatty acid profiles, in-hospital all-cause mortality, hospital-acquired infections, length of hospital/NICU stay, z scores and changes in z scores at discharge for weight, height and head circumference, time to full EN, duration of respiratory (mechanical, non-invasive) support, duration of inotropic support, the incidence of hyper and hypoglycaemia, incidence of metabolic acidosis, liver function, blood urea nitrogen, and C-reactive protein (CRP). Discussion This RCT will examine the effects of early versus late PN in term and late preterm infants by comparing key biochemical and clinical outcomes and has the potential to identify underlying pathways for beneficial or harmful effects related to the timing of commencement of PN in such infants. Trial registration ANZCTR; ACTRN12620000324910 (3rd March 2020)

In the present study we report the efficacy of two food supplements derived from olives in reducing lipid oxidation. To this end, 12 healthy volunteers received a single dose (25 mL) of olive phenolics, mainly hydroxytyrosol (HT), provided as a liquid dietary supplement (30.6 or 61.5 mg HT), followed by an investigation of two reliable markers of oxidative stress. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 h post-intake. Plasma-oxidized low-density lipoprotein (oxLDL) cholesterol levels were measured with ELISA using a monoclonal antibody, while F2-isoprostanes (F2-IsoPs) were quantified in urine with UHPLC-DAD-MS/MS. Despite the great variability observed between individuals, a tendency to reduce lipoxidation reactions was observed in the blood in response to a single intake of the food supplements. In addition, the subgroup of individuals with the highest baseline oxLDL level showed a significant (p < 0.05) decrease in F2-IsoPs at 0.5 and 12 h post-intervention. These promising results suggest that HT supplementation could be a useful aid in preventing lipoxidation. Additionally, people with a redox imbalance could benefit even more from supplementing with bioavailable HT. [ABSTRACT FROM AUTHOR]

Obesity affects over 40% of the adult population and is a major risk factor for morbidity and mortality due to cardiovascular disease. Black women have one of the highest prevalences of obesity, insulin resistance, hypertension, and cardiovascular events in the US. We previously found that free radical-mediated lipid peroxidation contributes to IL-6 production in dendritic cells leading to inflammation and hypertension. Thus, we hypothesized that F2-isoprostanes (F2-IsoPs), products and biomarkers of endogenous lipid peroxidation, contribute to increased inflammation and IL-6 production among obese Black women. We studied a total of 88 obese Black women of age 42.0 ± 9.8 years, weight 102 ± 16 kg, and body mass index (BMI) 37.68 ± 5.08. Systolic and diastolic blood pressure were 124 ± 14/76.2 ± 9.9 mmHg, heart rate was 68.31 ± 10.26 beats/min, and fasting insulin was 15.0 ± 8.7 uU/mL. Plasma F2-IsoPs were measured using gas chromatography/negative ion chemical ionization mass spectrometry (GC/NICI-MS). Plasma cytokines, including IL-6, IL-8, IL-10, IL-1β, TNF-a, and C-reactive proteins were measured using multiplex Luminex technology. Anthropometric measurements were performed using dual-energy X-ray absorptiometry. Using Pearson's correlation analysis, we found that BMI was positively correlated with plasma F2-IsoPs, while inversely correlated with insulin sensitivity in obese Black women. Further, F2-IsoPs were positively correlated with inflammatory marker IL-6 levels while negatively correlated with anti-inflammatory marker IL-10. In addition, we found that plasma F2-IsoPs levels were significantly associated with reduced insulin sensitivity. These results suggest that F2-IsoPs may be associated with obesity-induced cardiovascular risk in Black women by increasing the production of inflammatory cytokine IL-6 and decreasing the production of anti-inflammatory IL-10. [ABSTRACT FROM AUTHOR]

Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%–69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)- secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twenty-eight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation. Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress is hypothesized to contribute to the pathogenesis of several chronic diseases. Numerous dietary and lifestyle factors are associated with oxidative stress; however, little is known about associations of genetic factors, individually or jointly with dietary and lifestyle factors, with oxidative stress in humans.Methods: We genotyped 22 haplotype-tagging single nucleotide polymorphisms (SNPs) in 3 antioxidant enzyme (AE) genes and 79 SNPs in 14 DNA base excision repair (BER) genes to develop oxidative stress-specific AE and BER genetic risk scores (GRS) in two pooled cross-sectional studies (n = 245) of 30–74-year-old, White, cancer- and inflammatory bowel disease-free adults. Of the genotypes, based on their associations with a systemic oxidative stress biomarker, plasma F2-isoprostanes (FiP) concentrations, we selected 4 GSTP1 SNPs for an AE GRS, and 12 SNPs of 5 genes (XRCC1, TDG, PNKP, MUTYH, and FEN1) for a BER GRS. We also calculated a previously-reported, validated, questionnaire-based, oxidative stress biomarker-weighted oxidative balance score (OBS) comprising 17 anti- and pro-oxidant dietary and lifestyle exposures, with higher scores representing a higher predominance of antioxidant exposures. We used general linear regression to assess adjusted mean FiP concentrations across GRS and OBS tertiles, separately and jointly.Results: The adjusted mean FiP concentrations among those in the highest relative to the lowest oxidative stress-specific AE and BER GRS tertiles were, proportionately, 11.8% (p = 0.12) and 21.2% (p = 0.002) higher, respectively. In the joint AE/BER GRS analysis, the highest estimated mean FiP concentration was among those with jointly high AE/BER GRS. Mean FiP concentrations across OBS tertiles were similar across AE and BER GRS strata.Conclusion: Our pilot study findings suggest that DNA BER, and possibly AE, genotypes collectively may be associated with systemic oxidative stress in humans, and support further research in larger, general populations.

The urinary metabolites (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), an F2-isoprostane and biomarker of oxidative damage, and "prostaglandin E2 metabolite" (PGE-M), a biomarker of inflammation, are elevated in cigarette smokers. However, there is little information in the literature on the longitudinal stability of these widely used biomarkers. In a large clinical trial involving 10 institutional sites, smokers were given, free of charge over a period of 20 weeks, Spectrum NRC600/601 research cigarettes containing 15.5 mg nicotine/g tobacco. All participants were instructed to smoke these cigarettes for the duration of the study. At weeks 4, 8, 12, 16, and 20, first morning urine voids were collected and analyzed for 8-iso-PGF2α and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8-iso-PGF2α at Week 4 was 1.34 ± 1.08 (S.D.) pmol/mg creatinine (N = 226) while that of PGE-M was 73.7 ± 113 (S.D.) pmol/mg creatinine (N = 232). The corresponding levels at Week 20 were 1.35 ± 0.93 (S.D.) pmol/mg creatinine (N = 209) for 8-iso-PGF2α and 74.2 ± 142 (S.D.) pmol/mg creatinine (N = 210) for PGE-M. There was variation in these values in the intervening weeks. The intra-class correlation coefficients (ICC) were 0.51 (95% CI, 0.45, 0.57) and 0.36 (0.30, 0.43), for 8-iso-PGF2α and PGE-M, respectively, indicating fair longitudinal stability for 8-iso-PGF2α and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8-iso-PGF2α and PGE-M. These results indicate that, in addition to cigarette smoking, endogenous processes of oxidative damage and inflammation influence the levels of these biomarkers over time among current smokers.

Abstract Background African Americans (AAs) are disproportionately affected by cardiovascular disease (CVD), they are 20% more likely to die from CVD than whites, chronic exposure to inflammation and oxidative stress contributes to CVD. In previous studies, enhancing parasympathetic cholinergic activity has been shown to decrease inflammation. Considering that AAs have decreased parasympathetic activity compared to whites, we hypothesize that stimulating it with a central acetylcholinesterase (AChE) inhibitor, galantamine, would prevent lipid-induced oxidative stress. Objective To test the hypothesis that acute dose of galantamine, an AChE inhibitor, decreases lipid-induced oxidative stress in obese AAs. Methods Proof-of-concept, double-blind, randomized, placebo-controlled, crossover study that tested the effect of a single dose of 16 mg of galantamine versus placebo on lipid-induced oxidative stress in obese AAs. Subjects were studied on two separate days, one week apart. In each study day, 16 mg or matching placebo was administered before 20% intralipids infusion at doses of 0.8 mL/m2/min with heparin at doses of 200 U/h for 4 h. Outcomes were assessed at baseline, 2 and 4 h during the infusion. Main outcome measures Changes in F2-isoprostane (F2-IsoPs), marker of oxidative stress, measured in peripheral blood mononuclear cells (PBMC) and in plasma at baseline, 2, and 4-h post-lipid infusion. Secondary outcomes include changes in inflammatory cytokines (IL-6, TNF alpha). Results A total of 32 obese AA women were screened and fourteen completed the study (age 37.8 ± 10.70 years old, BMI 38.7 ± 3.40 kg/m2). Compared to placebo, 16 mg of galantamine significantly inhibited the increase in F2-IsoPs in PBMC (0.007 ± 0.008 vs. − 0.002 ± 0.006 ng/sample, P = 0.016), and plasma (0.01 ± 0.02 vs. − 0.003 ± 0.01 ng/mL, P = 0.023). Galantamine also decreased IL-6 (11.4 ± 18.45 vs. 7.7 ± 15.10 pg/mL, P = 0.021) and TNFα levels (18.6 ± 16.33 vs. 12.9 ± 6.16 pg/mL, P = 0.021, 4-h post lipid infusion) compared with placebo. These changes were associated with an increased plasma acetylcholine levels induced by galantamine (50.5 ± 10.49 vs. 43.6 ± 13.38 during placebo pg/uL, P = 0.025). Conclusions In this pilot, proof-of-concept study, enhancing parasympathetic nervous system (PNS) cholinergic activity with galantamine inhibited lipid-induced oxidative stress and inflammation induced by lipid infusion in obese AAs. Trial registration: ClinicalTrials.gov identifiers NCT02365285.

Patients with septic shock are under an intense inflammatory burden, which is closely associated with increased oxidative stress and depletion of antioxidants such as vitamin C. We hypothesized that patients with septic shock would present with elevated oxidative stress (assessed as F 2 -isoprostanes) and that administration of parenteral vitamin C to these patients would attenuate F 2 -isoprostane concentrations. We recruited 40 critically ill patients with septic shock into a randomized placebo-controlled trial and assessed the effect of short-term (4-day) parenteral vitamin C administration (100 mg/kg/d) on 8-isoprostane F 2α concentrations, which were measured using enzyme-linked immunosorbent assays. Sources of sepsis and intensive care unit severity scores were recorded. Smokers (n = 20) and nonsmoking controls (n = 50) were assessed for comparison. The median baseline 8-isoprostane F 2α concentration in the septic patients was 3.95 (interquartile range [Q1, Q3] 2.1, 6.63) ng/mg creatinine; this was higher than smokers 1.61 [1.25, 2.82] P =.007 ng/mg creatinine; P =.005) and nonsmoking controls 1.12 [0.76, 1.57] ng/mg creatinine; P <.0001). The 8-isoprostane F 2α concentrations in the placebo group did not vary significantly over the duration of the study. Although parenteral vitamin C administration significantly increased the vitamin C status of the patients within 24 hours, this did not affect their 8-isoprostane F 2α concentrations. In conclusion, patients with septic shock have elevated 8-isoprostane F 2α excretion, which short-term parenteral vitamin C administration is unable to attenuate. If vitamin C is to work by antioxidant mechanisms, then early administration, before the development of shock, may be required. This trial was registered at anzctr.org.au (ACTRN12617001184369). ELISA, enzyme-linked immunosorbent assay; HPLC, high-performance liquid chromatography. [Display omitted] [ABSTRACT FROM AUTHOR]

Although paraquat (PQ) induces oxidative damage and inflammatory responses in the lungs, the mechanism underlying PQ-induced acute kidney injury in patients is unclear. Immunosuppressive therapy with glucocorticoids and the immunosuppressant cyclophosphamide (CP) has been employed to treat patients with PQ poisoning. This study examined whether PQ could concurrently cause renal injury, inflammatory responses, and oxidative damage in the kidneys, and whether CP and dexamethasone (DEX) could suppress PQ-induced alterations. Mice were assigned to eight groups: Control, PQ, DEX, PQ plus DEX, CP, PQ plus CP, DEX plus CP, and PQ plus DEX with CP. DEX, CP, and DEX plus CP reversed PQ-induced renal injury, as indicated by urinary albumin-to-creatinine ratios and urea nitrogen levels in serum. The treatments also attenuated PQ-induced renal infiltration of leukocytes and macrophages and induction of the Il6 , Tnf , Icam , Cxcl2 , Tlr4 , and Tlr9 genes encoding the inflammatory mediators in the kidneys. However, DEX only partially suppressed the macrophage infiltration, whereas DEX plus CP provided stronger protection than DEX or CP alone for the induction of Il6 and Cxcl2. Moreover, through the detection of F 2 -isoprostanes (F 2 -IsoPs) and isofurans in the kidneys and lungs and F 2 -IsoPs in the plasma and urine, the therapies were found to suppress PQ-induced lipid peroxidation, although DEX was less effective. Finally, PQ decreased ubiquinol-9:ubiquinone-9 ratios in the kidneys. This effect of PQ was not found under CP treatment, but the ratio was lower than that of the control group. Our findings suggest that the suppression of PQ-induced inflammatory responses by DEX and CP in the kidneys can mitigate oxidative damage and acute kidney injury. [Display omitted] • Dexamethasone and cyclophosphamide (CP) are used to treat paraquat (PQ) poisoning. • Immunosuppressive therapy alleviated PQ-induced renal dysfunction in mice. • The therapy suppressed PQ-induced inflammatory responses in the kidneys. • PQ-induced elevation of renal F 2 -IsoPs and isofurans was suppressed by the therapy. • Lipid peroxidation increased by PQ in the lungs and body fluids was also inhibited. [ABSTRACT FROM AUTHOR]

Elena Moretti,1 Cinzia Signorini,1 Daria Noto,1 Sergio Antonio Tripodi,2 Andrea Menchiari,3 Ester Sorrentino,2 Giulia Collodel1 1Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; 2Department of Pathology Unit, AOUS Siena, Siena, Italy; 3Department of Business and Law, University of Siena, Siena, ItalyCorrespondence: Elena Moretti, Department of Molecular and Developmental Medicine, University of Siena, Siena, 53100, Italy, Tel +39 0577 232451, Email elena.moretti@unisi.itPurpose: Omentin-1/intelectin (ITLN)1 is an adipocytokine with both anti-inflammatory and anti-oxidative stress properties, and little is known about its role in male reproduction. This study was aimed at exploring the relationships among omentin-1/ITLN1, semen parameters and F2-isoprostanes (F2-IsoPs), a maker of oxidative stress, in groups of patients affected by different pathologies. In addition, omentin-1/ITLN1 immunolocalization was assessed in ejaculated spermatozoa and in tissues of male reproductive system.Patients and Methods: Semen samples of infertile patients with varicocele (n = 27), genitourinary infections (n = 17), idiopathic infertility (n = 15) and fertile men (n = 21) were analyzed following WHO guidelines, and seminal plasma were used to determine omentin-1/ITLN1 by ELISA and F2-IsoP levels by gas chromatography/negative-ion chemical ionization tandem mass spectrometry. Omentin-1/ITLN1 was localized in human sperm and in the tissue of male reproductive system.Results: Considering all participants, F2-IsoP and omentin-1/ITLN1 levels were positively correlated (p = 0.000), and both these indices were negatively correlated with sperm parameters. Infertile patients showed lower sperm parameters than fertile ones; varicocele and infection groups had significantly increased levels of F2-IsoPs (both p = 0.000) and omentin-1/ITLN1 (p = 0.000 and p = 0.001, respectively). Omentin-1/ITLN1 signal was located as a spot in the connecting piece (in 43.5% of cases midpiece was also labeled) of sperm from fertile men and in cytoplasmic residue and in the entire tail in sperm of patients with varicocele and genitourinary infections. A focal omentin-1/ITLN1 immunolabelling was evident in the basal area of epididymal tubule, and a diffuse signal was present in the seminal vesicle epithelium.Conclusion: Semen omentin-1/ITLN1 originates from seminal vesicles, its levels increase in inflammatory conditions and are negatively correlated with sperm parameters. For this reason, a sort of protective role of omentin-1/ITLN1 can be postulated, as this adipokine shows anti-inflammatory properties also in many other biological systems.Graphical Abstract: Keywords: adipocytokines, F2-isoprostanes, human sperm, immunocytochemistry, epididymis, seminal vesicles

Background: To reduce risk for intermittent hypoxia a high fraction of inspired oxygen is routinely used during anesthesia induction. This differs from the cautious dosing of oxygen during neonatal resuscitation and intensive care and may result in significant hyperoxia. Aim: In a randomized controlled trial, we evaluated oxygenation during general anesthesia with a low (23%) vs a high (80% during induction and recovery, and 40% during maintenance) fraction of inspired oxygen, in newborn infants undergoing surgery. Method: Thirty‐five newborn infants with postconceptional age of 35–44 weeks were included (17 infants in low and 18 in high oxygen group). Oxygenation was monitored by transcutaneous partial pressure of oxygen, pulse oximetry, and cerebral oxygenation. Predefined SpO2 safety targets dictated when to increase inspired oxygen. Results: At start of anesthesia, oxygenation was similar in both groups. Throughout anesthesia, the high oxygen group displayed significant hyperoxia with higher (difference−20.3 kPa, 95% confidence interval (CI)—28.4 to 12.2, p <.001) transcutaneous partial pressure of oxygen values than the low oxygen group. While SpO2 in the low oxygen group was lower (difference − 5.8%, 95% CI –9.3 to –2.4, p <.001) during anesthesia, none of the infants spent enough time below SpO2 safety targets to mandate supplemental oxygen, and cerebral oxygenation was within the normal range and not statistically different between the groups. Analysis of the oxidative stress biomarker urinary F2‐Isoprostane revealed no differences between the low and high oxygen group. Conclusion: We conclude that in healthy newborn infants, use of low oxygen during general anesthesia was feasible, while the prevailing practice of using high levels of inspired oxygen resulted in significant hyperoxia. The trade‐off between careful dosing of oxygen and risks of hypo‐ and hyperoxia in neonatal anesthesia should be further examined. [ABSTRACT FROM AUTHOR]

Early brain activity, measured using amplitude-integrated EEG (aEEG), is correlated with neurodevelopmental outcome in preterm newborns. F2-isoprostanes (IPs) are early biomarkers predictive for brain damage. We aimed to investigate the relationship between perinatal IPs concentrations and quantitative aEEG measures in preterm newborns. Thirty-nine infants (gestational age (GA) 24–27 ± 6 weeks) who underwent neuromonitoring using aEEG during the first two days after birth were enrolled. The rate of spontaneous activity transients per minute (SAT rate) and inter-SAT interval (ISI) in seconds were computed. Two postnatal time-points were examined: within 12 h (day 1) and between 24 and 48 h (day 2). IPs were measured in plasma from cord blood (cb-IPs) and between 24 and 48 h (pl-IPs). Multivariable regression analyses were performed to assess the correlation between IPs and brain activity. Cb-IPs were not associated with SAT rate and ISI at day 1. Higher pl-IPs were followed by longer ISI (R = 0.68; p = 0.034) and decreased SAT rate (R = 0.58; p = 0.007) at day 2 after adjusting for GA, FiO2 and IVH. Higher pl-IPs levels are associated with decreased functional brain activity. Thus, pl-IPs may represent a useful biomarker of brain vulnerability in high-risk infants. [ABSTRACT FROM AUTHOR]

Background: Despite the wide use of parenteral nutrition (PN) in neonatal intensive care units (NICU), there is limited evidence regarding the optimal time to commence PN in term and late preterm infants. The recommendations from the recently published ESPGHAN/ESPEN/ESPR/CPEN and NICE guidelines are substantially different in this area, and surveys have reported variations in clinical practice. The aim of this randomised controlled trial (RCT) is to evaluate the benefits and risks of early versus late PN in term and late preterm infants.Methods/design: This study is a single-centre, non-blinded RCT in the NICU of Perth Children's Hospital, Western Australia.A total of 60 infants born ≥34 weeks of gestation who have a high likelihood of intolerance to enteral nutrition (EN) for at least 3-5 days will be randomised to early (day 1 or day 2 of admission) or late commencement (day 6 of admission) of PN after informed parental consent. In both groups, EN will be commenced as early as clinically feasible. Primary outcomes are plasma phenylalanine and plasma F2-isoprostane levels on Day 4 and Day 8 of admission. Secondary outcomes are total and individual plasma amino acid profiles, plasma and red blood cell fatty acid profiles, in-hospital all-cause mortality, hospital-acquired infections, length of hospital/NICU stay, z scores and changes in z scores at discharge for weight, height and head circumference, time to full EN, duration of respiratory (mechanical, non-invasive) support, duration of inotropic support, the incidence of hyper and hypoglycaemia, incidence of metabolic acidosis, liver function, blood urea nitrogen, and C-reactive protein (CRP).Discussion: This RCT will examine the effects of early versus late PN in term and late preterm infants by comparing key biochemical and clinical outcomes and has the potential to identify underlying pathways for beneficial or harmful effects related to the timing of commencement of PN in such infants.Trial Registration: ANZCTR; ACTRN12620000324910 (3rd March 2020). [ABSTRACT FROM AUTHOR]

Purpose: Carotenoids may protect against chronic diseases including cancer and cardiometabolic disease by mitigating oxidative stress and/or inflammation. We cross-sectionally evaluated associations between carotenoids and biomarkers of oxidative stress or inflammation. Methods: From 2003 to 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35–74. Post-menopausal participants (n = 512) were randomly sampled to measure carotenoids and biomarkers of oxidative stress. Dietary carotenoid consumption was assessed using a validated 110-item Block 1998 food frequency questionnaire; use of β-carotene-containing supplements was also assessed. Plasma carotenoids were quantified, adjusting for batch. Urinary markers of lipid peroxidation, 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were also measured. Since the biomarker 8-iso-PGF2α can reflect both oxidative stress and inflammation, we used a modeled 8-iso-PGF2α to prostaglandin F2α ratio approach to distinguish effects reflecting oxidative stress versus inflammation. Multivariable linear regression was used to assess the associations of dietary and plasma carotenoids with the estimated biomarker concentrations. Results: Total plasma carotenoids were inversely associated with 8-iso-PGF2α-M concentrations (P for trend across quartiles = 0.009). Inverse trends associations were also seen for α-carotene and β-carotene. In contrast, lutein/zeaxanthin showed associations with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations. The inverse association for total carotenoids appeared to be specific for oxidative stress (chemical 8-iso-PGF2α; Phighest vs. lowest quartile = 0.04 and P for trend across quartiles = 0.02). The pattern was similar for α-carotene. However, lutein/zeaxanthin tended to have a stronger association with enzymatic 8-iso-PGF2α, suggesting an additional anti-inflammatory effect. Supplemental β-carotene was inversely associated with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations, as well as with both chemical and enzymatic 8-iso-PGF2α. Dietary carotenoids were not associated with either biomarker. Conclusion: Plasma carotenoids and supplemental β-carotene were associated with lower concentrations of 8-iso-PGF2α metabolite. Plasma carotenoids associations may reflect antioxidant effects. [ABSTRACT FROM AUTHOR]

This study aims to investigate the role of ferroptosis, an iron-dependent form of regulated cell death, in male infertility. The motivation behind this research stems from the increasing recognition of oxidative stress and iron metabolism dysregulation as critical factors in male reproductive health. In this study, 28 infertile patients (grouped by the presence of urogenital infections or varicocele) and 19 fertile men were selected. Spermiograms were performed by light microscopy (WHO, 2021). Testosterone, ferritin, transferrin-bound iron, transferrin, and F 2 -isoprostanes (F 2 -IsoPs) were detected in seminal plasma. Glutathione peroxidase 4 (GPX4) and acyl coenzyme A synthetase long chain family member 4 (ACSL4) were also assessed in sperm cells using enzyme-linked immunosorbent assays (ELISA). All the variables were correlated (statistically significant Spearman's rank correlations) in the whole population, and then the comparison between variables of the different groups of men were carried out. Seminal ferritin and transferrin positively correlated with seminal F 2 -IsoPs, which had positive correlations with ACSL4 detected in sperm cells. Ferritin and ACSL4 negatively correlated with the seminal parameters. No correlation was detected for GPX4. Comparing the variables in the three examined groups, elevated levels of ACSL4 were observed in infertile patients with urogenital infections and varicocele; GPX4 levels were similar in the three groups. These results suggested a mechanism of ferroptosis, identified by increased ACSL4 levels and the occurrence of lipid peroxidation. Such events appear to be GPX4-independent in reproductive pathologies such as varicocele and urogenital infections.

Background: African Americans (AAs) are disproportionately affected by cardiovascular disease (CVD), they are 20% more likely to die from CVD than whites, chronic exposure to inflammation and oxidative stress contributes to CVD. In previous studies, enhancing parasympathetic cholinergic activity has been shown to decrease inflammation. Considering that AAs have decreased parasympathetic activity compared to whites, we hypothesize that stimulating it with a central acetylcholinesterase (AChE) inhibitor, galantamine, would prevent lipid-induced oxidative stress. Objective: To test the hypothesis that acute dose of galantamine, an AChE inhibitor, decreases lipid-induced oxidative stress in obese AAs. Methods: Proof-of-concept, double-blind, randomized, placebo-controlled, crossover study that tested the effect of a single dose of 16 mg of galantamine versus placebo on lipid-induced oxidative stress in obese AAs. Subjects were studied on two separate days, one week apart. In each study day, 16 mg or matching placebo was administered before 20% intralipids infusion at doses of 0.8 mL/m2/min with heparin at doses of 200 U/h for 4 h. Outcomes were assessed at baseline, 2 and 4 h during the infusion. Main outcome measures: Changes in F2-isoprostane (F2-IsoPs), marker of oxidative stress, measured in peripheral blood mononuclear cells (PBMC) and in plasma at baseline, 2, and 4-h post-lipid infusion. Secondary outcomes include changes in inflammatory cytokines (IL-6, TNF alpha). Results: A total of 32 obese AA women were screened and fourteen completed the study (age 37.8 ± 10.70 years old, BMI 38.7 ± 3.40 kg/m2). Compared to placebo, 16 mg of galantamine significantly inhibited the increase in F2-IsoPs in PBMC (0.007 ± 0.008 vs. − 0.002 ± 0.006 ng/sample, P = 0.016), and plasma (0.01 ± 0.02 vs. − 0.003 ± 0.01 ng/mL, P = 0.023). Galantamine also decreased IL-6 (11.4 ± 18.45 vs. 7.7 ± 15.10 pg/mL, P = 0.021) and TNFα levels (18.6 ± 16.33 vs. 12.9 ± 6.16 pg/mL, P = 0.021, 4-h post lipid infusion) compared with placebo. These changes were associated with an increased plasma acetylcholine levels induced by galantamine (50.5 ± 10.49 vs. 43.6 ± 13.38 during placebo pg/uL, P = 0.025). Conclusions: In this pilot, proof-of-concept study, enhancing parasympathetic nervous system (PNS) cholinergic activity with galantamine inhibited lipid-induced oxidative stress and inflammation induced by lipid infusion in obese AAs. Trial registration: ClinicalTrials.gov identifiers NCT02365285. [ABSTRACT FROM AUTHOR]

Background: The current study aimed to investigate the Superoxide dismutase, Glutathione Peroxidase activity, Advanced oxidation Protein products levels, Malondialdehyde levels, Baseline Conjugated Diene concentration, and 8-Isoprostaglandin F2α (8-IPG-F2α) quantification in diabetic and non-diabetic senile cataract patients to find out the pathomechanism of early onset of cataract in diabetic patients. Methods: This case–control study was performed on 184 subjects undergoing cataract surgery. For 8-IPG-F2α quantification, 35 diabetics and non-diabetic lenses and the entire study included 22 patients with diabetic senile cataracts and non-diabetic senile cataracts of aqueous humor age ≥ 40 years. Ninety-two patients with diabetic senile cataract and non-diabetic senile cataract lenses aged ≥ 40 years were incorporated for all other studies. The student's t-test was used for statistical analysis. Results: From the study population, the mean age was 63.82 ± 0.6, and 75% of them were female. Higher female prevalence in both groups was observed. The results revealed that the superoxide dismutase and glutathione peroxidase activity were significantly reduced in diabetic patients compared to non-diabetic patients (p < 0.001) in both lenses and aqueous humor. Malondialdehyde, conjugated diene, and 8-IPG-F2α levels significantly increased in diabetic patients when compared to non-diabetic (p < 0.01), and advanced oxidation protein products levels also significantly increased in diabetic patients when compared to non-diabetics in both lenses and aqueous humor (p < 0.001). Conclusion: The current study revealed that oxidative stress and Lipid per-oxidation have an imperative role in the diabetic-related complication, specifically in the lens, may have a responsibility in the pathomechanism of early onset of cataracts coupled with diabetes mellitus. [ABSTRACT FROM AUTHOR]

The F2-isoprostane 8-iso-PGF 2α (also known as 15-F 2t -isoprostane, iPF 2α -III, 8-epi PGF 2α , 15(S)-8-iso-PGF 2α , or 8-Isoprostane), a thromboxane A 2 receptor (TP) agonist, stable biomarker of oxidative stress, and risk marker of cardiovascular disease, has been proposed to aggravate atherogenesis in genetic mouse models of atherosclerotic vascular disease. Moreover, the TP plays an eminent role in the pathophysiology of endothelial dysfunction, atherogenesis, and cardiovascular disease. Yet it is unknown, how the TP expressed by vascular cells affects atherogenesis or 8-iso-PGF 2α -related effects in mouse models of atherosclerosis. We studied Ldlr-deficient vascular endothelial-specific (EC) and vascular smooth muscle cell (VSMC)-specific TP knockout mice (TPECKO/Ldlr KO; TPVSMCKO/Ldlr KO) and corresponding wild-type littermates (TPWT/Ldlr KO). The mice were fed a Western-type diet for eight weeks and received either 8-iso-PGF 2α or vehicle infusions via osmotic pumps. Subsequently, arterial blood pressure, atherosclerotic lesion formation, and lipid profiles were analyzed. We found that VSMC-, but not EC-specific TP deletion, attenuated atherogenesis without affecting blood pressure or plasma lipid profiles of the mice. In contrast to a previous report, 8-iso-PGF 2α tended to reduce atherogenesis in TPWT/Ldlr KO and TPEC KO/Ldlr KO mice, again without significantly affecting blood pressure or lipid profiles of these mice. However, no further reduction in atherogenesis was observed in 8-iso-PGF 2α -treated TPVSMC KO/Ldlr KO mice. Our work suggests that the TP expressed in VSMC but not the TP expressed in EC is involved in atherosclerotic lesion formation in Ldlr-deficient mice. Furthermore, we report an inhibitory effect of 8-iso-PGF 2α on atherogenesis in this experimental atherosclerosis model, which paradoxically appears to be related to the presence of the TP in VSMC. [Display omitted] • VSMC-specific TP knockout (KO) reduces atherogenesis in Ldlr KO mice. • EC-specific TP KO in Ldlr KO mice does not affect atherosclerotic lesion formation. • 8-iso-PGF 2a infusion moderately reduces atherogenesis in Ldlr KO mice. • Neither TP KO nor 8-iso-PGF 2α infusion affect blood pressure or plasma lipid levels. [ABSTRACT FROM AUTHOR]

In this review, the role of fatty acids (FA) in human pathological conditions, infertility in particular, was considered. FA and FA-derived metabolites modulate cell membrane composition, membrane lipid microdomains and cell signaling. Moreover, such molecules are involved in cell death, immunological responses and inflammatory processes. Human health and several pathological conditions are specifically associated with both dietary and cell membrane lipid profiles. The role of FA metabolism in human sperm and spermatogenesis has recently been investigated. Cumulative findings indicate F2 isoprostanes (oxygenated products from arachidonic acid metabolism) and resolvins (lipid mediators of resolution of inflammation) as promising biomarkers for the evaluation of semen and follicular fluid quality. Advanced knowledge in this field could lead to new scenarios in the treatment of infertility. [ABSTRACT FROM AUTHOR]

The increasing proportion of older citizens in our society reflects a need to better understand age-related biological underpinnings of mood, as depression in older age may be under-diagnosed. Pre-clinical and human studies evidence a relationship between oxidative stress (OS) biomarkers in depression symptoms, and an influence of biological factors such as Body Mass Index (BMI), but focus has been clinical or younger samples, and less is known about patterns in healthy older adults. We investigated these associations with data derived from the Australian Research Council Longevity Study (ARCLI; ANZCTR12611000487910), in 568 healthy adults aged 60–75 years using F2-Isoprostanes plasma levels, and controlling for demographic factors, in assessing mood via the Beck Depression Inventory-II, Chalder Fatigue Scale, and General Health Questionnaire 12. Elevated F2-Isoprostanes contributed to depressed mood on the BDI-II and reduced general health on the GHQ-12. BMI was positively associated with Chalder Fatigue scores, yet better ratings on the GHQ-12. Females had significantly higher F2-Isoprostanes than males. The results suggest that in otherwise healthy older adults, mood and mental health are reduced with increases in oxidative stress markers, exhibiting similar patterns observed in clinical groups. Sex as a factor should be considered when assessing OS levels in systemic pathologies. BMI as a modifiable risk factor for maintenance of mental health, and OS modification through nutrient supplementation, are discussed. The findings contribute to understanding oxidative stress marker patterns in healthy older adults and their potential role in mood symptoms and mental health. [ABSTRACT FROM AUTHOR]

Purpose: Plasma F2-isoprostanes (FiP) concentration, a reliably measured, valid, systemic oxidative stress biomarker, has been associated with multiple health-related outcomes; however, associations of most individual dietary and lifestyle exposures with FiP are unclear, and there is no reported oxidative balance score (OBS) comprising multiple dietary and/or lifestyle components weighted by their associations with FiP. Methods: To investigate cross-sectional associations of dietary and lifestyle characteristics with plasma FiP concentrations, we used multivariable general linear models to compare adjusted mean FiP concentrations across categories of dietary nutrient and whole-food intakes and lifestyle characteristics in two pooled cross-sectional studies (n = 386). We also developed equal-weight and weighted OBS (nutrient- and foods-based dietary OBS, lifestyle OBS, and total OBS), and compared adjusted mean FiP concentrations across OBS tertiles. Results: Among men and women combined, adjusted mean FiP concentrations were statistically significantly, proportionately 28.1% higher among those who were obese relative to those who were normal weight; among those in the highest relative to the lowest total nutrient intake tertiles, FiP concentrations were statistically significantly lower by 9.8% for carotenes, 13.6% for lutein/zeaxanthin, 10.9% for vitamin C, 12.2% for vitamin E, 11.5% for glucosinolates, and 5% for calcium. Of the various OBS, the weighted OBS that combined total nutrient intakes and lifestyle exposures was most strongly associated with FiP concentrations: among those in the highest relative to the lowest total OBS, mean FiP concentrations were statistically significantly 29.7% lower (P < 0.001). Conclusion: Multiple dietary and lifestyle characteristics, individually, and especially collectively, may contribute to systemic oxidative stress. [ABSTRACT FROM AUTHOR]

Oxylipins are powerful signalling compounds derived from polyunsaturated fatty acids (PUFAs) and involved in regulating the immune system response. A mass spectrometry-based method was developed and validated for the targeted profiling of 52 oxylipins (e.g., isoprostanoids, prostaglandins, epoxy- and hydroxy-fatty acids, specialized pro-resolving mediators) and 4 PUFAs in small urinary extracellular vesicles (uEVs). Ultrasound-assisted extraction using a 50:50 v/v MeOH:H 2 O mixture ensured optimal analytical performances. Limits of detection ranged between 10 and 400 pg/mL for oxylipins and 0.10–3 ng/mL for PUFAs. Satisfactory recoveries (85–116 %) and good intra- and inter-day precisions (RSD ≤15 %) were obtained for all the analytes. The reliability of the procedure was tested in a real case scenario by monitoring ultramarathon runners during the world Tor des Géants® (TDG) race. Both F 2 - and E 2 -isoprostanes were detected in small uEVs of the ultramarathon runners, suggesting the onset of an oxidant insult. 5-F 2t -IsoP exhibited significant pre- to post-race variations, thus potentially representing a non-invasive marker of in-vivo lipid peroxidation. The presence of specialized pro-resolving mediators suggests the activation of pro-resolution signalling cascade resolving inflammation. These outcomes may help manage post-exercise recovery and improve training. [Display omitted] • Oxylipins and their precursors are monitored in urinary extracellular vesicles. • Ultrasound-assisted extraction guarantees satisfying analytical performances. • Isoprostanoids are detected for the first time in urinary extracellular vesicles. • 5-F 2t -isoprostane significantly changes pre- to post-ultramarathon race. • Specialized pro-resolving mediators are released in ultramarathon runners. [ABSTRACT FROM AUTHOR]

BackgroundOxidative stress is implicated in both depression and anxiety, but it is currently unclear whether this relates to syndromal diagnoses or trans-diagnostic dimensional symptoms. We examined the relationship between oxidative stress and severity of depression and anxiety symptoms in individuals with Major Depressive Disorder (MDD).MethodsPlasma oxidative stress markers F2-isoprostanes and oxidized glutathione (GSSG), and the antioxidant reduced glutathione (GSH), were assessed in 69 physically healthy, medication-free MDD subjects. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety (HAM-A) and Hamilton Depression (HAM-D) Rating Scales. Total HAM-A and HAM-D scores, along with "core" anxiety and depression subscales, and individual HAM-D items "psychic anxiety" and "depressed mood," were related to oxidative stress markers. Analyses controlled for age, sex, BMI, and smoking.ResultsTotal HAM-A ratings were positively associated with F2-isoprostanes (β=.26, p=.042) and GSSG (β=.25, p=.049), but not GSH (β=.05, p=.711). Core anxiety severity was positively associated with F2-isoprostanes (β=.34, p=.012) and GSSG, although this did not reach significance (β=.24, p=.074). None of the biological markers were significantly associated with total HAM-D or core depression ratings (all p>.13). Subjects scoring high on "psychic anxiety" had elevated F2-isoprostanes (p=.030) and GSSG (p=.020). This was not seen with "depressed mood" scores (all p>.12).LimitationsWe assessed peripheral oxidative markers, but their relationship to the brain is unclear.ConclusionsOxidative stress is more closely related to anxiety than depression symptoms in MDD. This highlights the importance of relating oxidative stress to specific symptoms and could provide new insights into the biological correlates of affective disorders.

BACKGROUND: Schizophrenia is one of the most disabling psychiatric disorders with increased morbidity and mortality. Both schizophrenia and oxidative stress have been associated with accelerated aging. Previous studies found increased oxidative stress in individuals with schizophrenia, though only one study measured F2-isoprostanes and did so in urine. To our knowledge, the present study is the first to assess plasma F2-isoprostane levels, the putative gold standard measure of systemic oxidative stress in vivo, in schizophrenia. METHODS: We compared plasma F2-isoprostane levels in 134 stable outpatients with schizophrenia and 120 age- and gender-matched healthy comparison (HC) subjects. Sociodemographic and clinical data were collected in both groups. RESULTS: Plasma F2-isoprostane levels were significantly higher in the schizophrenia group than in the HC group. Women had higher F2-isoprostane levels compared to men, and those with higher body mass index (BMI) had higher levels, within each group. F2-isoprostane levels correlated with BMI, physical functioning, and medical comorbidity but not with severity of psychopathology or executive function. Linear models showed significant effects of diagnosis, gender, and BMI on F2-isoprostane levels, but no interactions. DISCUSSION: Our finding of increased oxidative stress in schizophrenia is consistent with reports of increased morbidity and mortality as well as accelerated aging in schizophrenia. The significant associations between F2-isoprostane levels and both gender and BMI warrant further study.

BackgroundSchizophrenia is one of the most disabling psychiatric disorders with increased morbidity and mortality. Both schizophrenia and oxidative stress have been associated with accelerated aging. Previous studies found increased oxidative stress in individuals with schizophrenia, though only one study measured F2-isoprostanes and did so in urine. To our knowledge, the present study is the first to assess plasma F2-isoprostane levels, the putative gold standard measure of systemic oxidative stress in vivo, in schizophrenia.MethodsWe compared plasma F2-isoprostane levels in 134 stable outpatients with schizophrenia and 120 age- and gender-matched healthy comparison (HC) subjects. Sociodemographic and clinical data were collected in both groups.ResultsPlasma F2-isoprostane levels were significantly higher in the schizophrenia group than in the HC group. Women had higher F2-isoprostane levels compared to men, and those with higher body mass index (BMI) had higher levels, within each group. F2-isoprostane levels correlated with BMI, physical functioning, and medical comorbidity but not with severity of psychopathology or executive function. Linear models showed significant effects of diagnosis, gender, and BMI on F2-isoprostane levels, but no interactions.DiscussionOur finding of increased oxidative stress in schizophrenia is consistent with reports of increased morbidity and mortality as well as accelerated aging in schizophrenia. The significant associations between F2-isoprostane levels and both gender and BMI warrant further study.

Anna Dietrich-Muszalska,1 Joanna Kolodziejczyk-Czepas,2 Pawel Nowak2 1Medical University of Lodz, Department of Biological Psychiatry and Neurophysiology, Lodz, Poland; 2University of Lodz, Department of General Biochemistry, Lodz, PolandCorrespondence: Anna Dietrich-MuszalskaDepartment of Biological Psychiatry and Neurophysiology Medical University of Lodz, Lodz, 92-215, Poland, Mazowiecka 6/8 Tel +691881787Fax +48 42 2725652Email tzn_lodz@post.plPurpose: Evidence that antipsychotic drugs (ADs) can affect oxidative stress estimated with various biomarkers in schizophrenic patients is controversial and limited. Therefore, in the present study, we assessed the ability of six atypical ADs (clozapine, olanzapine, quetiapine, risperidone, aripiprazole, and ziprasidone) used in schizophrenia treatment to modulate oxidative damage to different biomolecules such as lipids and proteins.Patients and Methods: We measured the levels of oxidative stress markers in plasma and urine: total antioxidant capacity by FRAP (according to a modified method of Benzie & Strain), thiobarbituric acid reactive species – TBARS (spectrophotometric method), 4-hydroxy-2-nonenal (4-HNE) (OxiSelect™ HNE Adduct Competitive ELISA Kit), 3-nitrotyrosine (3-NT) (OxiSelect™ Nitrotyrosine ELISA Kit) in plasma, and F2-isoprostanes (BIOXYTECH® Urinary 8-epi-Prostaglandin F2α) in the urine of 60 schizophrenic patients (before and after treatment) and in 30 healthy subjects.Results: Our results showed that in schizophrenic patients levels of lipid peroxidation markers (TBARS, F2-isoprostanes) were higher than in healthy subjects but FRAP in schizophrenic patients was lower than in healthy controls and increased after 4-week treatment with tested ADs. A 4-week treatment with ADs caused the improvement of psychopathology symptoms estimated by Positive and Negative Syndrome Scale (PANSS) that was accompanied by decreased lipid peroxidation (F2-isoprostanes, TBARS; p=2.9x10− 6, p=7.6x10− 5, respectively) and an increase in total antioxidative capacity (FRAP) (p=5.16x10− 16).Conclusion: Atypical antipsychotics especially clozapine, olanzapine and quetiapine demonstrate the effective outcome of antipsychotic treatment, beneficial antioxidative action by reducing lipid peroxidation and increased total plasma antioxidant activity.Keywords: schizophrenia, antipsychotics, F2-isoprostanes, TAC, other oxidative markers

This study aimed to assess the effect of Vitamin C on blood pressure (BP), and subsequently on oxidative stress and nitric oxide (NO) release, following the low-intensity exercise in the patients. This study included 24 patients with type 2 diabetes mellitus (T2D) (age, 53 ± 7 years; hemoglobin A1c, 10.1% ± 0.9%) randomized into two 6-week daily arms based on the consumption of either placebo or 1000 mg Vitamin C. The crossover trial occurred after a 6-week washout. Before and after both supplementation arms, all patients performed cycling exercise at 33% of peak oxygen consumption for 20 min. BP was measured before, immediately, and 60 min after the exercise. Blood samples were drawn immediately before and after the exercise to determine plasma ascorbate, malondialdehyde (MDA), F2-isoprostanes (F2-IsoPs), and NO concentrations. Data showed significant lower BP in the Vitamin C arm when compared with the placebo arm (systolic BP [SBP] P < 0.001 at every time point, diastolic BP [DBP] P < 0.001 except at immediately after exercise, P < 0.05). Plasma ascorbate concentration (P < 0.05 at every time point) and plasma NO (at resting P < 0.001, immediately after exercise P < 0.05) were significantly increased in the Vitamin C arm than in the placebo arm. Plasma MDA (P < 0.05 at every time point) and F2-IsoPs (P < 0.05 at every time point) concentrations were significantly lower in the Vitamin C arm than in the placebo arm. In addition, data showed significantly lower SBP (P < 0.001 at every time point), DBP (P < 0.001 except at immediately after exercise P < 0.05), plasma MDA (P < 0.001 at every time point), and F2-IsoPs (P < 0.05 at every time point) at post-supplementation than at pre-supplementation. Besides, there were significantly higher plasma ascorbate (P < 0.05 at every time point) and NO (at rest P < 0.01, immediately after exercise P < 0.05) concentrations at post-supplementation than at pre-supplementation. This is in contrast to the placebo treatment arm which demonstrated no statistical difference in all outcomes throughout the experiment. This study suggests that 6-week Vitamin C supplementation decreased preexercise and postexercise BPs, possibly due to improved oxidative stress and NO release. However, exercise had no effect on any outcome measures.

Dioxin-like pollutants (DLPs), such as polychlorinated biphenyl 126 (PCB 126), are synthetic chemicals classified as persistent organic pollutants. They accumulate in adipose tissue and have been linked to cardiometabolic disorders, including fatty liver disease. The toxicity of these compounds is associated with activation of the aryl hydrocarbon receptor (Ahr), leading to the induction of phase I metabolizing enzyme cytochrome P4501a1 (Cyp1a1) and the subsequent production of reactive oxygen species (ROS). Recent research has shown that DLPs can also induce the xenobiotic detoxification enzyme flavin-containing monooxygenase 3 (FMO3), which plays a role in metabolic homeostasis. We hypothesized whether genetic deletion of Fmo3 could protect mice, particularly in the liver, where Fmo3 is most inducible, against PCB 126 toxicity. To test this hypothesis, male C57BL/6 wild-type (WT) mice and Fmo3 knockout (Fmo3 KO) mice were exposed to PCB 126 or vehicle (safflower oil) during a 12-week study, at weeks 2 and 4. Various analyses were performed, including hepatic histology, RNA-sequencing, and quantitation of PCB 126 and F2-isoprostane concentrations. The results showed that PCB 126 exposure caused macro and microvesicular fat deposition in WT mice, but this macrovesicular fatty change was absent in Fmo3 KO mice. Moreover, at the pathway level, the hepatic oxidative stress response was significantly different between the two genotypes, with the induction of specific genes observed only in WT mice. Notably, the most abundant F2-isoprostane, 8-iso-15-keto PGE2, increased in WT mice in response to PCB 126 exposure. The study's findings also demonstrated that hepatic tissue concentrations of PCB 126 were higher in WT mice compared to Fmo3 KO mice. In summary, the absence of FMO3 in mice led to a distinctive response to dioxin-like pollutant exposure in the liver, likely due to alterations in lipid metabolism and storage, underscoring the complex interplay of genetic factors in the response to environmental toxins. • FMO3 deletion results in differential lipid distribution after PCB 126 exposure. • Liver transcriptomics revealed more changes in wildtype mice due to PCB 126. • Hepatic Gsta4 and Gstm6 expression were induced only in wildtypes by PCB 126. • F2-isoprostane, 8-iso-15-keto PGE2, was increased only in wildtype mice. • Wildtypes displayed higher hepatic PCB 126 concentration compared to knockouts. [ABSTRACT FROM AUTHOR]

In the present study we report the efficacy of two food supplements derived from olives in reducing lipid oxidation. To this end, 12 healthy volunteers received a single dose (25 mL) of olive phenolics, mainly hydroxytyrosol (HT), provided as a liquid dietary supplement (30.6 or 61.5 mg HT), followed by an investigation of two reliable markers of oxidative stress. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 h post-intake. Plasma-oxidized low-density lipoprotein (oxLDL) cholesterol levels were measured with ELISA using a monoclonal antibody, while F2-isoprostanes (F2-IsoPs) were quantified in urine with UHPLC-DAD-MS/MS. Despite the great variability observed between individuals, a tendency to reduce lipoxidation reactions was observed in the blood in response to a single intake of the food supplements. In addition, the subgroup of individuals with the highest baseline oxLDL level showed a significant (p < 0.05) decrease in F2-IsoPs at 0.5 and 12 h post-intervention. These promising results suggest that HT supplementation could be a useful aid in preventing lipoxidation. Additionally, people with a redox imbalance could benefit even more from supplementing with bioavailable HT.

Neurodegenerative diseases and chronic cigarette smoking are associated with increased cerebral oxidative stress (OxS). Elevated F2-isoprostane levels in biological fluid is a recognized marker of OxS. This study assessed the association of active cigarette smoking with F2-isoprostane in concentrations in cognitively-normal elders (CN), and those with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD). Smoking and non-smoking CN (n = 83), MCI (n = 164), and probable AD (n = 101) were compared on cerebrospinal fluid (CSF) iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostane concentrations. Associations between F2-isoprostane levels and hippocampal volumes were also evaluated. In CN and AD, smokers had higher iPF2α-III concentration; overall, smoking AD showed the highest iPF2α-III concentration across groups. Smoking and non-smoking MCI did not differ on iPF2α-III concentration. No group differences were apparent on 8,12, iso-iPF2α-VI concentration, but across AD, higher 8,12, iso-iPF2α-VI level was related to smaller left and total hippocampal volumes. Results indicate that active cigarette smoking in CN and probable AD is associated with increased central nervous system OxS. Further investigation of factors mediating/moderating the absence of smoking effects on CSF F2-isoprostane levels in MCI is warranted. In AD, increasing magnitude of OxS appeared to be related to smaller hippocampal volume. This study contributes additional novel information to the mounting body of evidence that cigarette smoking is associated with adverse effects on the human central nervous system across the lifespan.

BackgroundCigarette smoking generates reactive oxidant species and contributes to systemic oxidative stress, which plays a role in the pathophysiology of chronic diseases. Nutrients with antioxidant properties, including vitamin E and selenium, are proposed to reduce systemic oxidative burden and thus to mitigate the negative health effects of reactive oxidant species.ObjectiveOur objective was to determine whether long-term supplementation with vitamin E and/or selenium reduces oxidative stress in smokers, as measured by urine 8-iso-prostaglandin F2-alpha (8-iso-PGF2α).DesignWe measured urine 8-iso-PGF2α with competitive enzyme linked immunoassay (ELISA) in 312 male current smokers after 36 months of intervention in a randomized placebo-controlled trial of vitamin E (400IU/d all rac-α-tocopheryl acetate) and/or selenium (200µg/d L-selenomethionine). We used linear regression to estimate the effect of intervention on urine 8-iso-PGF2α, with adjustments for age and race.ResultsCompared to placebo, vitamin E alone lowered urine 8-iso-PGF2α by 21% (p=0.02); there was no effect of combined vitamin E and selenium (intervention arm lower by 9%; p=0.37) or selenium alone (intervention arm higher by 8%; p=0.52).ConclusionsLong-term vitamin E supplementation decreases urine 8-iso-PGF2α among male cigarette smokers, but we observed little to no evidence for an effect of selenium supplementation, alone or combined with vitamin E.

Hydrogen sulfide is a highly toxic gas-second only to carbon monoxide as a cause of inhalational deaths. Its mechanism of toxicity is only partially known, and no specific therapy exists for sulfide poisoning. We show in several cell types, including human inducible pluripotent stem cell (hiPSC)-derived neurons, that sulfide inhibited complex IV of the mitochondrial respiratory chain and induced apoptosis. Sulfide increased hydroxyl radical production in isolated mouse heart mitochondria and F2-isoprostanes in brains and hearts of mice. The vitamin B12 analog cobinamide reversed the cellular toxicity of sulfide, and rescued Drosophila melanogaster and mice from lethal exposures of hydrogen sulfide gas. Cobinamide worked through two distinct mechanisms: direct reversal of complex IV inhibition and neutralization of sulfide-generated reactive oxygen species. We conclude that sulfide produces a high degree of oxidative stress in cells and tissues, and that cobinamide has promise as a first specific treatment for sulfide poisoning.

Elevated oxidant levels and low antioxidant levels in patients with end-stage renal disease (ESRD) play a significant role in the development of endothelial dysfunction, atherogenesis and cardiovascular disease (CVD). A deficiency in vitamin D (Vit.D) is also suggested to be responsible for the generation of oxidative stress (OS) and CVD. Among dialysis patients, conflicting data exist concerning the relationship between hepatitis C virus (HCV) infection and OS. We studied the relationship between 25Vit.D level, HCV infection, and plasma 8 iso-prostaglandin F2 α (8-ISO-PGF2α) as an OS marker in an Egyptian hemodialysis (HD) cohort. One hundred and twenty ESRD patients on HD were initially recruited to the study but only 88 patients have met the inclusion and none of the exclusion criteria. Midweek predialysis session blood samples were collected for the measurement of 25(OH) Vit.D, plasma 8-ISO-PGF2α, high sensitivity C – reactive protein (hs-CRP), and intact parathyroid hormone (intact PTH). Patients were stratified into two groups according to the presence or absence of serum antibodies against HCV and their plasma 8-ISO-PGF2α were compared. Vit.D deficiency was noted in 93% of the participants; the median 8-ISO-PGF2α level was 382 pg/mL. No significant correlation between Vit.D and 8-ISO-PGF2α levels was found. Thirty-two participants (36%) were HCV+ and their 8-ISO-PGF2α levels were significantly lower relative to in the seronegative group (median 171 vs. 647 pg/mL; P < 0.006). In this Egyptian HD cohort, Vit D deficiency was highly prevalent, yet failed to show any correlation with F2-isoprostanes. HCV+ HD patients might be shielded from OS. [ABSTRACT FROM AUTHOR]

Brief Background Oxidative stress is increased in diabetes mellitus due to excessive production of oxygen free radicals and a deficiency in antioxidant mechanism. F2-isoprostanes are primary end products of lipid peroxidation and are considered to be a biological marker for assessing oxidative stress in tissues. This study aims to evaluate the level of salivary F2-isoprostane in type II diabetic patients and compare it with non-diabetic individuals. Materials and Methods A total of 150 subjects were included in the study comprising of 50 patients with controlled diabetes (Group I), 50 patients with uncontrolled diabetes (Group II) and 50 non-diabetic individuals (Group III). We analyzed the salivary F2 -isoprostane in these subjects using a sandwich ELISA technique. The data was analyzed using SPSS software version 16.0. One way ANOVA was used for the comparison of salivary F2-isoprostane levels among the study groups and Scheffe multiple comparison analysis was used to compare the level of isoprostane between the groups. P-value of less than 0.05 was considered to be statistically significant. Results Salivary F2-isoprostane levels were significantly higher in patients with uncontrolled diabetes compared to controlled diabetes (p<0.01). Non-diabetic individuals showed lower levels of salivary F2 isoprostanes compared to diabetic patients and were found to be statistically significant (p<0.01). Discussion Salivary isoprostanes are reliable markers to assess oxidative damage in patients with diabetes mellitus and hence anti oxidants can be initiated at an early stage to prevent complications. Summary and Conclusions The result of the study indicates that salivary F2- isoprostane can be used as a valuable marker of oxidative stress in diabetic patients. [ABSTRACT FROM AUTHOR]

Resistance to oxidative stress is reduced with age but there is lack of data regarding sex differences. In general, many sex differences are driven by sex hormones and thus might be expected to be lessened after menopause and at older ages. Aerobic fitness has been shown to increase redox capacity in older adults but whether adaptations differ between men and women is unknown. The aim of this study was to investigate sex differences and the association between redox capacity and aerobic fitness. Healthy men (n=20 and women (n=17) ages 60-86y participated in this study. Maximal oxygen consumption was measured with a graded exercise test on a cycle ergometer. Resistance to oxidative stress was measured by F2-isoprostane (F2-isoP) response to forearm ischemia/reperfusion (I/R) trial. The I/R trial elicited a significant F2-isoP response in the cohort as a whole (p

Background & aims: Plasma concentrations of bilirubin, a product of heme catabolism formed by biliverdin reductase A (BVRA), inversely associate with the risk of metabolic diseases including hepatic steatosis and diabetes mellitus in humans. Bilirubin has antioxidant and anti-inflammatory activities and may also regulate insulin signaling and peroxisome proliferator-activated receptor alpha (PPARα) activity. However, a causal link between bilirubin and metabolic diseases remains to be established. Here, we used the global Bvra gene knockout (Bvra–/–) mouse as a model of deficiency in bilirubin to assess its role in metabolic diseases. Approach & results: We fed mice fat-rich diets to induce hepatic steatosis and insulin resistance. Bile pigments were measured by LC-MS/MS, and hepatic lipids by LC-MS/MS (non-targeted lipidomics), HPLC-UV and Oil-Red-O staining. Oxidative stress was evaluated measuring F2-isoprostanes by GC-MS. Glucose metabolism and insulin sensitivity were verified by glucose and insulin tolerance tests, ex vivo and in vivo glucose uptake, and Western blotting for insulin signaling. Compared with wild type littermates, Bvra–/– mice contained negligible bilirubin in plasma and liver, and they had comparable glucose metabolism and insulin sensitivity. However, Bvra–/– mice exhibited an inflamed and fatty liver phenotype, accompanied by hepatic accumulation of oxidized triacylglycerols and F2-isoprostanes, in association with depletion of α-tocopherol. α-Tocopherol supplementation reversed the hepatic phenotype and observed biochemical changes in Bvra–/– mice. Conclusions: Our data suggests that BVRA deficiency renders mice susceptible to oxidative stress-induced hepatic steatosis in the absence of insulin resistance.

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. F 2 -isoprostanes (F 2 -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 F 2 -IsoPs rather than the unmetabolized F 2 -IsoPs to quantify oxidative damage in certain settings. Yet, the metabolism of F 2 -IsoPs is incompletely understood. This study sought to identify and characterize novel phase II metabolites of 15-F 2t -IsoP and 5-epi-5-F 2t -IsoP, two abundantly produced F 2 -IsoPs, in human liver microsomes (HLM). Utilizing liquid chromatography-mass spectrometry, we demonstrated that glucuronide conjugates are the major metabolites of these F 2 -IsoPs in HLM. Further, we showed that these molecules are metabolized by specific UGT isoforms. 15-F 2t -IsoP is metabolized by UGT1A3, 1A9, and 2B7, while 5-epi-5-F 2t -IsoP is metabolized by UGT1A7, 1A9, and 2B7. We identified, for the first time, the formation of intact glucuronide F 2 -IsoPs in human urine and showed that F 2 -IsoP glucuronidation is reduced in people supplemented with eicosapentaenoic and docosahexaenoic acids for 12 weeks. These studies demonstrate that endogenous F 2 -IsoP levels can be modified by factors other than redox mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To examine the associations between risk of pre‐eclampsia and pregnancy levels of maternal 25‐hydroxyvitamin D (25[OH]D) and oxidative stress biomarkers. Methods: A nested case–control study (n = 99; 34 cases; 65 controls) within a prospective pregnancy cohort. Maternal 25(OH)D and oxidative stress markers (six isomers of F2‐isoprostanes; F2‐isoPs) were measured in plasma at 12–18 and 24–26 gestational weeks. Vitamin D deficiency was defined as 25[OH]D less than 50 nmol/L. Results: Maternal vitamin D deficiency was associated with increased 8‐iso‐PGF2α (P = 0.037), 15(R)‐PGF2α (P = 0.004), (±)5‐iPF2α‐VI (P = 0.026) at 12–18 weeks. Vitamin D deficiency was inversely associated with 8‐iso‐PGF2α (P = 0.019) and (±)5‐iPF2α‐VI isomer (P = 0.010) at 24–26 weeks. Both maternal vitamin D deficiency (adjusted odds ratio [aOR], 4.79; 95% confidence interval [CI], 1.67–13.75) and increased (±)5‐iPF2α‐VI (aOR, 2.46; 95% CI, 1.16–5.22) at 24–26 weeks were associated with risk of pre‐eclampsia. However, the interaction test between 25(OH)D and (±)5‐iPF2α‐VI was not significant (P = 0.143). Conclusion: Plasma 25(OH)D below 50 nmol/L was associated with increased oxidative stress levels during pregnancy as measured by two F2‐isoP isomers, including the well‐studied marker 8‐iso‐PGF2α. Whether vitamin D‐induced oxidative stress mediates the risk of pre‐eclampsia warrants future study. Synopsis: In pregnancy, plasma 25‐hydroxyvitamin D levels lower than 50 nmol/L were associated with both increased oxidative stress measured as F2‐isoprostanes and increased risk of pre‐eclampsia. [ABSTRACT FROM AUTHOR]

Background/study context: F2-Isoprostanes are putative markers of oxidative stress, one of the processes associated with biological senescence. Evidence exists for elevated F2-Isoprostanes in chronic conditions including psychiatric disorders. Few studies have examined the relationship between oxidative stress and mood in older healthy samples, to establish the influence on mental health. Given current aging demographics in many nations, management of brain and mental health is crucial for longevity, chronic disease management, and quality of life. Method: We investigated the relationship between F2-Isoprostanes, a marker for oxidative stress, and anxiety and mood in 262 healthy adults aged 60–75 years, using baseline data from the Australian Research Council Longevity Intervention (ARCLI; ANZCTR12611000487910), a 12-month nutraceutical intervention study. Results: Higher F2 levels significantly predicted increased Depression-dejection and Anger-hostility subscale scores from the Profile of Mood States (POMS). Fatigue-inertia subscale was predicted by increased Body Mass Index. Spielberger State-Trait Inventory (STAI) scores were significantly higher in females. Conclusion: While the primary outcome data did not find a definitive relationship between F2 and total mood or general anxiety levels, the sub-scale data adds weight toward growing literature that biological processes such as oxidative stress are in part related to mood. This is a modifiable risk factor contributing to physical and mental wellbeing that are crucial to healthy aging. [ABSTRACT FROM AUTHOR]

Purpose: Perturbations in redox homeostasis can lead to physiological dysfunction and impaired stress resilience. This randomized controlled trial investigated whether aerobic exercise training could improve redox stress resilience measured by the response to a non-exercise redox stressor (forearm ischemia/reperfusion; I/R trial) in young and older men and women. We hypothesized that older adults would have impaired responses to redox perturbations, but that exercise training would reverse the dysfunction. Methods: Young (18-28yo, n=21) and older (60-77yo, n=19) men and women were randomized to 8-week exercise training (ET; 3 d/wk, 45 min/day) or a non-exercise control group (CON). Aerobic capacity was measured by VO2 peak test on a cycle ergometer. Plasma F2-isoprostane responses to the I/R trial were measured across 7 time points: pre-trial, and 15-, 30-, 60-, 120-, 180-, and 240-minutes post-trial. The I/R trial was completed before and after the 8-week exercise intervention or control arm. Results: There were no significant differences in I/R trial responses across age, sex, or groups randomized to training or control. Exercise training significantly improved I/R trial response compared to controls (p

Early brain activity, measured using amplitude-integrated EEG (aEEG), is correlated with neurodevelopmental outcome in preterm newborns. F2-isoprostanes (IPs) are early biomarkers predictive for brain damage. We aimed to investigate the relationship between perinatal IPs concentrations and quantitative aEEG measures in preterm newborns. Thirty-nine infants (gestational age (GA) 24–27 ± 6 weeks) who underwent neuromonitoring using aEEG during the first two days after birth were enrolled. The rate of spontaneous activity transients per minute (SAT rate) and inter-SAT interval (ISI) in seconds were computed. Two postnatal time-points were examined: within 12 h (day 1) and between 24 and 48 h (day 2). IPs were measured in plasma from cord blood (cb-IPs) and between 24 and 48 h (pl-IPs). Multivariable regression analyses were performed to assess the correlation between IPs and brain activity. Cb-IPs were not associated with SAT rate and ISI at day 1. Higher pl-IPs were followed by longer ISI (R = 0.68; p = 0.034) and decreased SAT rate (R = 0.58; p = 0.007) at day 2 after adjusting for GA, FiO2 and IVH. Higher pl-IPs levels are associated with decreased functional brain activity. Thus, pl-IPs may represent a useful biomarker of brain vulnerability in high-risk infants.

The present study evaluates the effect of olive (Olea europaea L.) vegetation water on human cells regarding its antioxidant properties and radical scavenger bioactivities. To this aim, two food supplements containing concentrated olive water in combination with 6% lemon juice or 70% grape juice, respectively, were assessed in different oxidation assays. From the investigated polyphenols, hydroxytyrosol, present in olives and in a lesser extent in grapes, was found to be the most abundant in both formulations, followed by tyrosol and oleuropein for the olive-derived concentrate with lemon juice, and by proanthocyanidins and tyrosol for the olive concentrate with grape juice. Cellular studies suggest that both formulations are effective antioxidants. In particular, the combination of olive and grape extracts showed a remarkable superoxides-, hydroxyl radicals-, and hydrogen peroxides-scavenging activity, while the formulation containing 94% olive concentrate wasmore potent in protecting the cells against lipoxidation. Both products showed a significant and similar effect in preventing advanced glycation end products' (AGEs) formation. In addition, preliminary data indicate that hydroxytyrosol is absorbed into the human body when administered via these hydrophilic matrices, as confirmed by the urinary excretion of free hydroxytyrosol. Since the availability of phytochemicals largely depends on the vehicle in which they are solved, these findings are of relevance and contribute to supporting the healthful effects here assessed in a cellular environment. [ABSTRACT FROM AUTHOR]

The study evaluated the uses of food additives in commercial cocoa beverages, and examined the effects of the food additives on their antioxidant and anti-inflammatory activities. The food additive lists of the cocoa beverage items on the shelves and chillers of ten randomly selected local supermarkets were recorded. The total flavonoid, polyphenol contents, and radical scavenging activity of the beverages were determined using the modified Dowd, Folin-Ciocalteu, and 1,1-diphenyl-2-picrylhydrazyl radical scavenging assays, respectively. Cellular experiments examined the inhibition of F2-isoprostanes, lipid hydroperoxides, leukotriene B4 productions, and myeloperoxidase activity by freshly isolated human neutrophils. The effects of food additives on the measured outcomes were evaluated. Food additives were added to 72% of the twenty five cocoa beverage products. Flavorings (60%), antioxidants (56%), pH regulators (40%), emulsifiers (36%), and colorings (4%) were added into these beverages. The cocoa beverages contained significant amounts of flavonoids, polyphenols, and radical-scavenging antioxidants. Their ethanolic extracts inhibited F2-isoprostanes, lipid hydroperoxides, leukotriene B4 productions, and myeloperoxidase activity from freshly isolated human neutrophils. After stratification by different food additive groups, the flavonoids, polyphenols contents, radical scavenging capacity, cellular inhibitions of F2-isoprostanes, lipid hydroperoxides, leukotriene B4, and myeloperoxidase activity were significantly increased by the beverages containing added antioxidants compared to those without. The other additive types did not influence the measured antioxidant and anti-inflammatory outcomes. Commercial cocoa beverages were shown to exert potential nutraceutical properties, such as antioxidant and anti-inflammatory activities. Selective food additives may exert profound effects on these properties by modulating the availability of flavonoids and polyphenols. [ABSTRACT FROM AUTHOR]

BackgroundCigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F2-isoprostane biomarkers of OxS.MethodsElders with a lifetime history of smoking (smokers; n=50; 75±5 years of age; 34±28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n=61; 76±6 years of age) on CSF iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostanes levels. F2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated.ResultsSmokers showed higher iPF2α-III level than never-smokers. An age×smoking status interaction was observed for 8,12, iso-iPF2α-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF2α-VI concentration was associated with smaller hippocampal volume, and greater iPF2α-III level was related to greater pack years.ConclusionsThis is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F2-isoprostane levels and greater age-related increases in F2-isoprostanes, and that higher F2-isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation.