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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 F2-isoprostanes (F2-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 F2-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.

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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:H2O 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 F2- and E2-isoprostanes were detected in small uEVs of the ultramarathon runners, suggesting the onset of an oxidant insult. 5-F2t-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.

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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.

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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.

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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 ßQ4vsQ1: - 0.17, 95% CI - 0.27, - 0.08; DASH ßQ4vsQ1: - 0.18, 95% CI - 0.28, - 0.08; aHEI ßQ4vsQ1: - 0.20, 95% CI - 0.30, - 0.10; HEI-2015 ßQ4vsQ1: - 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.

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Grape consumption acts on the immune system to produce antioxidant and anti-inflammatory effects. Since immune activity demonstrates circadian rhythmicity, with peak activity occurring during waking hours, the timing of grape intake may influence the magnitude of its antioxidant effect. This study followed a 2 × 2 factorial randomized, controlled design wherein healthy men and women (n = 32) consumed either a grape or placebo drink with a high-fat meal in the morning or evening. Urine was collected for measurements of biomarkers of oxidative stress and grape metabolites at baseline and post-meal at hour 1 and hours 1-6. F-2 isoprostane levels showed main effects of time period (baseline < hour 1 < hours 1-6, p < 0.0001), time (a.m. > p.m., p = 0.008) and treatment (placebo > grape, p = 0.05). Total F2-isoprostane excretion expressed as % baseline was higher in the a.m. vs. p.m. (p = 0.004) and in the a.m. placebo vs. all other groups (p < 0.05). Tartaric acid and resveratrol excretion levels were higher in the grape vs. placebo group (p < 0.05) but were not correlated with F-2 isoprostane levels. The findings support a protective effect of grape consumption against morning sensitivity to oxidative stress.

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Oxidative stress plays a central role in atherogenesis, implicated in endothelial dysfunction, coronary plaque formation, and destabilization. Therefore, identifying oxidative stress in the vascular wall by reliable biomarkers could aid in early diagnosis and better coronary artery disease (CAD) prognostication. Because of the short half-life of reactive oxygen species, the current approach is to measure stable products generated by the oxidation of macromolecules in plasma or urine. Most popular oxidative stress biomarkers are oxidized low-density lipoprotein, myeloperoxidase and lipid peroxidation biomarkers, such as malondialdehyde and F2-isoprostanes. Oxidative protein modification biomarkers and oxidized phospholipids have also been studied and discussed in the present review. Most of these biomarkers are associated with the presence and extent of CAD, are elevated in patients with acute coronary syndromes, and may predict outcomes independent of traditional CAD risk factors. However, further standardization of measurement methods and assessment in large randomized clinical trials are required to integrate these biomarkers into clinical practice. In addition, evidence that these biomarkers detect oxidative stress in the vascular wall lacks and more specific biomarkers should be developed to identify vascular oxidative stress. Consequently, several oxidative stress biomarkers have been developed, most of which can be associated with the presence and extent of CAD and event prognosis. However, they still have significant limitations that hinder their integration into clinical practice.

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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.

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Green tea extract (GTE) is a potential mitigator of oxidative stress, and F2-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 F2-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 F2-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 F2-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 F2-isoprostanes concentrations. Likewise, the COMT genotype did not modify the effect of GTE supplementation on F2-isoprostanes concentrations.

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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.

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We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F4-Neuroprostanes and F2-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (n=11), obesity (n=7) and overweight/obesity+GDM (n=7) groups. F4-Neuroprostanes and F2-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM. Lower content of F2-Isoprostanes suggests adaptive placental responses in GDM attenuating oxidative stress. However, low levels of placental F4-Neuroprostanes may indicate impaired DHA metabolism in GDM, affecting fetal development and offspring health. These results were not related to differences in placental content of DHA, AA and polyunsaturated fatty acids status nor to maternal diet or gestational weight gain. Placental DHA and AA metabolism differs in obesity and GDM, highlighting the importance of investigating the signalling roles of F4-Neuroprostanes and F2-Isoprostanes in the human term placenta.

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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)-ß, 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-ß 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-ß 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.

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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 F2-isoprostanes) and that administration of parenteral vitamin C to these patients would attenuate F2-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 F2α 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 F2α 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 F2α 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 F2α concentrations. In conclusion, patients with septic shock have elevated 8-isoprostane F2α 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).

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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.

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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).

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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 F2-isoprostanes (F2-IsoPs) and isofurans in the kidneys and lungs and F2-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.

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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.

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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.

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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.

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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.