8-isoprostane Levels Research Articles

Evaluation of Ocular and Systemic Oxidative Stress Markers in Patients with Diabetic Retinopathy

Proliferative diabetic retinopathy (PDR) is the most severe complication of chronic hyperglycaemi stimulates oxidative stress that changes the retinal basement membrane function and provokes neovascularization, macular edema and retinal detachment. But an oxidative–antioxidant biomarker assessment in ocular matrices, such as aqueous humor (AH) and vitreous, might show the oxidative stress (OS) status in the posterior segment. Here, we show a cross-sectional analytical study of 39 patients who had a vitrectomy and assess the levels of different oxidative–antioxidant biomarkers in blood, aqueous and vitreous humor in three groups: diabetes mellitus 2 (DM2) with PDR [DM(+)PDR(+)] (n =13), DM2 without PDR [DM(+)PDR(−)] (n = 13) and non-DM2 non-PDR [DM(−)PDR(−)] as the control group (n = 13). Our finding suggests the presence of oxidative stress in diabetic retinopathy, as evidenced by increased levels of 8-isoprostanes and decreased levels of total antioxidant capacity from stages before the development of diabetic retinopathy. Our results reveal a notable increment in catalase levels in the DM(+)PDR(+) group in blood and vitreous humor. Likewise, we identified that the DM(+)PDR(−) group presents significant levels in 8-IP and SOD in vitreous humor and blood versus aqueous humor. These finding suggest the role of antioxidant enzymes in compensating oxidative stress mechanisms in PDR development.

Effects of Time-Restricted Eating on Body Composition, Biomarkers of Metabolism, Inflammation, Circadian System and Oxidative Stress in Overweight and Obesity: An Exploratory Review.

Obesity is a chronic, complex and multi-factorial condition with an increasing prevalence worldwide. Irregular eating schedules might be a contributing factor to these numbers through the dysregulation of the circadian system. Time-restricted eating (TRE), an approach that limits eating windows, has been studied as a strategy to treat obesity, aligning eating occasions with metabolic circadian rhythms. This review aims to provide an overview of the impact of TRE protocols on metabolic, inflammatory, oxidative stress, and circadian rhythm biomarkers in people with overweight or obesity. Most studies report significant weight loss following TRE protocols. While glucose levels decreased in nearly all TRE interventions, only a few studies demonstrated statistically significant differences when compared to the control groups. The findings for CRP and TNF-α were inconsistent, with limited significant differences. Changes in lipid profile changes were variable and generally did not reach statistical significance. Both 4-hour and 6-hour TRE interventions significantly reduced 8-isoprostane levels. Additionally, TRE significantly altered clock gene expression, as well as that of genes associated with metabolic regulation in subcutaneous adipose tissue. While the evidence is still inconsistent, limiting eating to a consistent daily window of 8 to 12 hours can improve insulin sensitivity, reduce blood glucose, cholesterol and triglyceride levels and promote weight loss. These effects are likely attributable to both direct metabolic impacts and indirect benefits from weight loss and improved dietary habits. However, data on circadian, inflammatory, and specific metabolic biomarkers remain scarce and occasionally contradictory, highlighting the need for further research on these interventions.

Probiotics' supplementation alleviates disease severity and improves postural balance by repairing intestinal leak in patients suffering from osteoarthritis: a double-blinded clinical trial.

Increased intestinal leakiness and associated systemic inflammation are potential contributors to osteoarthritis (OA) and postural imbalance in the geriatric population. To date, no successful treatment to correct postural imbalance in OA is known. We aimed to explore the effects of a multistrain probiotic upon postural imbalance in OA-affected patients. In this randomised, double-blind trial with a placebo group, 147 patients suffering from knee OA (age span = 64-75 years) were divided into placebo (n 75) and probiotics (n 72) study groups. Vivomix 112 billion, multistrain probiotic was given once a day for 12 weeks. The outcomes of study variables were determined first at baseline and later after 12 weeks of intervention. These were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee flexion range of motion (ROM), pain intensity by visual analogue scale, handgrip strength (HGS), gait speed and balance control assessed in standing, semi-tandem and tandem stances. We determined plasma zonulin to determine intestinal leak along with c-reactive protein and 8-isoprostanes levels. A total of 136 OA patients taking placebo (n 71) and probiotics (n 65) were analysed. The probiotics group exhibited a reduction in pain intensity, disease severity and WOMAC scores along with improvement in balance scores, HGS and walking speed (P < 0·05 for all), no change in ROM, resting pain and 8-isoprostanes levels. The correlation analysis revealed a robust association of balance scores with plasma markers of intestinal leakiness and inflammation in probiotics but not in the placebo group. Probiotics reduce postural imbalance in OA patients partly due to a reduction in intestinal leakiness.

Antioxidant and anticoagulant properties of myo-inositol determined in an ex vivo studies and gas chromatography analysis

Myo-inositol plays a key role in the vasculature and may be beneficial for preventing harmful environmental effects. In this study aortic rings were isolated from middle-aged (12-month-old) male Wistar rats and preincubated with myo-inositol (0.01–100 mg/L) for 2 h. A stable thromboxane A2 analog was added (0.1 nM, 2 h) to analyze vascular dysfunction. The concentration of myo-inositol in the organ baths was determined via gas chromatography. In another experiment, human blood plasma was subjected to pro-oxidant - hydrogen peroxide administration, and myo-inositol was added to analyze lipid and protein oxidation processes. The thromboplastin time, prothrombin time, and thrombin time were also studied. Myo-inositol administration protected thiol groups against oxidative stress, meanwhile decreased vascular contraction and potentiated vasodilation (concentrations 1–100 mg/L, but not ≤ 0.1 mg/L), and changed the level of 8-isoprostane (concentrations: 0.1–100 mg/L, but not 0.01 mg/L) in plasma treated with H2O2/Fe2+. A dose above 100 mg/L additionally protected lipids (measured as thiobarbituric acid reactive substances) and increased thrombin time. Moreover, significant differences in vascular relaxation were observed between the studied myo-inositol concentrations (1 vs. 10 vs. 100 mg/L), which was not detected under the 0.1 mg/L. The concentration of myo-inositol in the organ baths determined via gas chromatography revealed that this nutraceutical agent was not used by the aortic rings during the incubation period in physiological processes. A protective effect of myo-inositol against prooxidant damage to human plasma and rat thoracic arteries has been demonstrated.

Effect of Time-Restricted Eating on Circulating Levels of IGF1 and Its Binding Proteins in Obesity: An Exploratory Analysis of a Randomized Controlled Trial.

This study aimed to investigate the effects of TRE on plasma IGF1, IGFBP1, IGFBP2, and IGFBP3, and whether these effects were mediated by weight loss or body composition changes. Insulin sensitivity, glucose control, adipokines, and inflammatory markers were also examined. An exploratory analysis of an 8-week randomized controlled trial implementing a daily TRE intervention was carried out. This study was conducted at the University of Illinois at Chicago in 2019. Participants with obesity were randomized to 4 or 6 h TRE (n = 35) or a control (n = 14) group. Plasma biomarkers were measured by ELISA at baseline and week 8. In a sub-analysis, participants were stratified into higher- (>3.5%) and lower- (≤3.5%) weight-loss groups. Participants fasted daily from 7 p.m. to 3 p.m. in the 4 h TRE group (20 h) and from 7 p.m. to 1 p.m. in the 6 h TRE group (18 h), followed by ad libitum eating for the remainder of the day. Controls received no dietary recommendations. IGF1, IGFBPs, hsCRP, and adipokines were the main outcome measures of this analysis. Repeated measures ANOVA and mediation analysis were conducted. Body weight significantly decreased with TRE (-3.6 ± 0.3%), contrasting with controls (+0.2 ± 0.5%, p < 0.001). Significant effects of TRE over time were observed on plasma IGFBP2, insulin, HOMA-IR, and 8-isoprostane levels, without affecting other biomarkers. In the sub-analysis, IGFBP2 increased while leptin and 8-isoprostane decreased significantly only in the "higher weight loss" subgroup. Changes in insulin and HOMA-IR were related to TRE adherence. Eight-week daily 4 to 6 h TRE did not affect IGF1, IGFBP1, or IGFBP3 levels but improved insulin, HOMA-IR, and 8-isoprostane. IGFBP2 increased and leptin decreased when weight loss exceeded 3.5% of baseline.

Carvedilol through ß1-Adrenoceptor blockade ameliorates glomerulonephritis via inhibition of oxidative stress, apoptosis, autophagy, ferroptosis, endoplasmic reticulum stress and inflammation

Glomerulonephritis (GN) is one of the main causes of end stage renal disease and requires an effective treatment for inhibiting GN. Renal nerves through efferent (RENA) and afferent (RANA) innervation to glomeruli regulate the glomerular function. We delineated the role of RENA and RANA on anti-Thy1.1-induced GN. Female Wistar rats were divided into Control, Thy1.1 plus anti-Thy1.1, bilaterally renal nerve denervation (DNX) plus anti-Thy1.1, and topical capsaicin to bilateral renal nerves for selective ablation of RANA (DNAX) plus anti-Thy1.1. We examined RANA and RENA response to anti-Thy1.1 and compared the effect of DNX or DNAX on urinary oxidative stress, renal gp91, tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), apoptosis, autophagy, ferroptosis, antioxidant enzymes, endoplasmic reticulum (ER) stress and inflammation by western blot. Anti-Thy1.1 significantly enhanced RENA, but did not affect RANA. DNX significantly decreased TH and CGRP expression, whereas DNAX only reduced CGRP expression. Anti-Thy1.1 significantly increased glomerulosclerosis injury, urinary protein, electron paramagnetic resonance signals of alpha-(4-pyridyl-N-oxide)-N-tert-butylnitrone adducts, 8-isoprostane and nitrotyrosine levels, NADPH oxidase gp91phox (gp91), macrophage/monocyte (ED-1), GRP-78, Beclin-1/LC3-II, Bax/caspase-3/poly(ADP-ribose) polymerase expression, inflammatory cytokines levels and decreased renal Copper/Zinc superoxide dismutase, Cystine/glutamate transporter (xCT) and Glutathione peroxidase 4 (GPX4) expression vs. Control. The enhanced oxidative parameters or reduced antioxidant defense by anti-Thy1.1 were significantly attenuated by DNX but not DNAX. Additionally, oral ß1-adrenoceptor antagonist-Carvedilol at an early stage reduced anti-Thy1.1 increased proteinuria level and oxidative parameters. Our data suggest that DNX and ß1-adrenoceptor antagonist-Carvedilol efficiently attenuate oxidative stress, inflammation, ER stress, autophagy, ferroptosis and apoptosis in GN.

Neuroprotective Actions of Hydrogen Sulfide-Releasing Compounds in Isolated Bovine Retinae

Background: We have evidence that hydrogen sulfide (H2S)-releasing compounds can reduce intraocular pressure in normotensive and glaucomatous rabbits by increasing the aqueous humor (AH) outflow through the trabecular meshwork. Since H2S has been reported to possess neuroprotective actions, the prevention of retinal ganglion cell loss is an important strategy in the pharmacotherapy of glaucoma. Consequently, the present study aimed to investigate the neuroprotective actions of H2S-releasing compounds against hydrogen peroxide (H2O2)-induced oxidative stress in an isolated bovine retina. Materials and Methods: The isolated neural retinae were pretreated with a substrate for H2S biosynthesis called L-cysteine, with the fast H2S-releasing compound sodium hydrosulfide, and with a mitochondrial-targeting H2S-releasing compound, AP123, for thirty minutes before a 30-min oxidative insult with H2O2 (100 µM). Lipid peroxidation was assessed via an enzyme immunoassay by measuring the stable oxidative stress marker, 8-epi PGF2α (8-isoprostane), levels in the retinal tissues. To determine the role of endogenous H2S, studies were performed using the following biosynthesis enzyme inhibitors: aminooxyacetic acid (AOAA, 30 µM); a cystathione-β-synthase/cystathionine-γ-lyase (CBS/CSE) inhibitor, α–ketobutyric acid (KBA, 1 mM); and a 3-mercaptopyruvate-s-sulfurtransferase (3-MST) inhibitor, in the absence and presence of H2S-releasing compounds. Results: Exposure of the isolated retinas to H2O2 produced a time-dependent (10–40 min) and concentration-dependent (30–300 µM) increase in the 8-isoprostane levels when compared to the untreated tissues. L-cysteine (10 nM–1 µM) and NaHS (30 –100 µM) significantly (p &lt; 0.001; n = 12) prevented H2O2-induced oxidative damage in a concentration-dependent manner. Furthermore, AP123 (100 nM–1 µM) attenuated oxidative H2O2 damage resulted in an approximated 60% reduction in 8-isoprostane levels compared to the tissues treated with H2O2 alone. While AOAA (30 µM) and KBA (1 mM) did not affect the L-cysteine evoked attenuation of H2O2-induced oxidative stress, KBA reversed the antioxidant responses caused by AP123. Conclusions: In conclusion, various forms of H2S-releasing compounds and the substrate, L-cysteine, can prevent H2O2-induced lipid peroxidation in an isolated bovine retina.

Taming hemoglobin chemistry—a new hemoglobin-based oxygen carrier engineered with both decreased rates of nitric oxide scavenging and lipid oxidation

The clinical utility of hemoglobin-based oxygen carriers (HBOC) is limited by adverse heme oxidative chemistry. A variety of tyrosine residues were inserted on the surface of the γ subunit of recombinant fetal hemoglobin to create novel electron transport pathways. This enhanced the ability of the physiological antioxidant ascorbate to reduce ferryl heme and decrease lipid peroxidation. The γL96Y mutation presented the best profile of oxidative protection unaccompanied by loss of protein stability and function. N-terminal deletions were constructed to facilitate the production of recombinant hemoglobin by fermentation and phenylalanine insertions in the heme pocket to decrease the rate of NO dioxygenation. The resultant mutant (αV1del. αL29F, γG1del. γV67F, γL96Y) significantly decreased NO scavenging and lipid peroxidation in vitro. Unlike native hemoglobin or a recombinant control (αV1del, γG1del), this mutation showed no increase in blood pressure immediately following infusion in a rat model of reperfusion injury, suggesting that it was also able to prevent NO scavenging in vivo. Infusion of the mutant also resulted in no meaningful adverse physiological effects apart from diuresis, and no increase in oxidative stress, as measured by urinary isoprostane levels. Following PEGylation via the Euro-PEG-Hb method to increase vascular retention, this novel protein construct was compared with saline in a severe rat reperfusion injury model (45% blood volume removal for 90 minutes followed by reinfusion to twice the volume of shed blood). Blood pressure and survival were followed for 4 h post-reperfusion. While there was no difference in blood pressure, the PEGylated Hb mutant significantly increased survival.

Relationships of 8 - Isoprostane and Vitamin K Levels With Blood Clotting Time In Last Stage of Hepatocellular Carcinoma Patients

Liver diseases are one of the most serious life-threatening diseases , and among the most important of these diseases is hepatocellular carcinoma, which poses a future challenge to public health. the goal of this work is to explore the existence association between the decrease level of vitamin K and an increase level of 8-isoprostane With a high rate of blood clotting time . The (PT ( in all patients it was high, and rate ranged from ( 21.00 -25.00), while in all the control group was normal . we also found that patients who suffer from HCC substantially reduced levels of VK2, The mean levels of Human VK2 were 135.78 ± 17.15 and 170.69 ± 18.15, in HCC patients / control respectively, However, Mean levels of Human 8-Isoprostane were 3436.44 ± 894.45 and 2389.13 ± 439.66, in HCC patients / control respectively; mean level turns out that it highly significant higher than in HCC patients compare to control . It is concluded that low levels of this vitamin in HCC patients may make liver cells less able to fend off the invasion and spread of cancer cells, while high levels of Human 8-Isoprostane raise the danger of HCC illness in ill individuals and, consequently, increase the risk of death.

Associations between APOE genotypes, urine 8-isoprostane and blood trace elements in middle-aged mothers (CROME study)

BackgroundThere is almost no data on the combined associations between apolipoprotein E gene (APOE) genotypes, trace elements (TEs), and lipid peroxidation in vivo. The aim of our study was to evaluate the association between APOE genotypes and TE levels in blood (B-TEs) and erythrocytes (E-TEs), and 8-isoprostane in urine (U-8-isoprostane) in women with low exposure to potentially toxic TEs and with adequate supply of essential TEs. MethodsB-TEs, E-TEs and U-8-isoprostane were determined in 172 healthy women of childbearing age (30.1–51.4 years) using ICP-MS and ELISA competitive assay, respectively. All women were divided into three APOE genotype groups according to the presence of the ɛ4 allele, ɛ2 allele or ɛ3 homozygotic allele. The associations between B-TEs, E-TE, U-8-isoprostane, and the APOE genotype groups were estimated by multiple variable linear regression models with relevant explanatory variables (e.g., age, BMI, and seafood). ResultsAll TE and U-8-isoprostane levels were inside the reference ranges for the healthy population. In the multiple variable linear regression models, our results showed that urine 8-isoprostane levels increased by up to 43.3% in the APOE4 group compared to the APOE3 group and a negligible negative modifying effect for essential TEs. However, the APOE genotype groups were associated also with some TEs. A clear positive association was found between the APOE2 and APOE4 groups (vs. APOE3) with B-molybdenum. ConclusionsOur study suggests that the APOE4 genotype played an important role in 8-isoprostane variability in a population with an adequate supply of essential and with low exposure to potentially toxic TEs. Adequate copper, zinc and selenium status seemed to be protective against, while the levels of nonessential TEs were probably too low to play a decisive role in 8-isoprostane formation. The observed impact of the APOE2 and APOE4 groups on increased B-molybdenum opens a new research topic.

Anti-Platelet Activity of Sea Buckthorn Seeds and Its Relationship with Thermal Processing.

Sea buckthorn (Hippophae rhamnoides L.) is a tree or shrub with small, orange berries. Sea buckthorn seeds have shown many properties beneficial to human health, including antioxidant, anti-hypertensive, anti-hyperlipidemic, and retinoprotective activities. Seeds, as a component of food, are often exposed to high temperatures, which can increase or decrease their biological activity. In our previous study, we showed that both raw and roasted sea buckthorn seeds had significant antioxidant activity, which was measured in human plasma in vitro. In this paper, we evaluated the effect of extracts from raw and roasted sea buckthorn seeds on several parameters of hemostasis in vitro, including thrombus formation in full blood (measured by the Total Thrombus formation Analysis System-T-TAS), blood platelet activation (based on the exposition of P-selectin, the active form of GPIIb/IIIa on their surface and platelet-derived microparticles formation), aggregation (measured with impedance aggregometry), adhesion to fibrinogen and collagen, arachidonic acid metabolism in washed platelets stimulated by thrombin, and COX-1 activity. We also measured the levels of free 8-isoprostane in plasma and the total non-enzymatic antioxidant status of plasma. The extract from roasted seeds (50 µg/mL) significantly prolonged the time of occlusion measured by T-TAS-the AUC10 (area under the curve) value was decreased by approximately 18%. Both extracts decreased the exposition of the active form of GPIIb/IIIa on the surface of platelets activated with 10 μM ADP (by 38.4-62.2%) and 20 μM ADP (by 39.7-51.3%). Moreover, the extract from raw seeds decreased the exposition of P-selectin on the surface of platelets stimulated with 20 μM ADP (by 31.2-34.9%). The adhesion of thrombin-stimulated platelets to fibrinogen and collagen was inhibited only by the extract from roasted sea buckthorn seeds (by 20-30%). Moreover, the extract from raw seeds inhibited the level of TBARS (thiobarbituric acid-reactive substances, an indicator of enzymatic peroxidation of arachidonic acid) in washed platelets stimulated with thrombin; the activity of COX-1 was inhibited by both extracts, although the effect of the extract from raw seeds was stronger. These results indicate that sea buckthorn seeds have anti-platelet activity that is not decreased by thermal processing, but more research is needed to determine which exact chemical compounds and mechanisms are responsible for this phenomenon.

The Impact of the Reduction in Environmental Pollution during COVID-19 Lockdown on Healthy Individuals.

The lockdown imposed to combat the COVID-19 pandemic produced a historic fall in air pollution in cities like Barcelona. This exceptional situation offered a unique context in which to examine the effects of air pollutants on human health. The present study aims to determine and compare the oxidative stress biomarkers Th1/Th2 and inflammatory-related cytokines in healthy individuals first during lockdown and then six months after the easing of the restrictions on mobility. A prospective study of a representative sample of 58 healthy, non-smoking adults was carried out. During lockdown and six months post-easing of restrictions, blood samples were drawn to measure the percentage of eosinophils, levels of Th1/Th2 and inflammatory-related cytokines assessed by a multiplex assay (BioRad Laboratories S.A., Marnes-la-Coquette, France), and levels of 8-isoprostane, glutathione peroxidase activity, and myeloperoxidase (Cayman Chemical Co., Ann Arbor, MI, USA), to assess their value as biomarkers of oxidative stress. Six months after easing mobility restrictions, increases in the levels of 8-isoprostane (p < 0.0001), IL-1β (p = 0.0013), IL-1ra (p = 0.0110), IL-4 (p < 0.0001), IL-13 (p < 0.0001), G-CSF (p = 0.0007), and CCL3 (p < 0.0001) were recorded, along with reductions in glutathione peroxidase (p < 0.0001), IFN-γ (p = 0.0145), TNFα (p < 0.0001), IP-10 (p < 0.0001), IL-2 (p < 0.0001), IL-7 (p < 0.0001), basic FGF (p < 0.0001), CCL4 (p < 0.0001), and CCL5 (p < 0.0001). No significant differences were observed in the rest of the biomarkers analyzed. The reduction in environmental pollution during the COVID-19 lockdown significantly lowered the levels of oxidative stress, systemic inflammation, and Th2-related cytokines in healthy people.

The effect of air pollution on selected immune system parameters, 8-isoprostane, and alpha-1-antitrypsin of people living in environmentally distinct regions

BackgroundAir pollution is associated with adverse health effects, especially on the respiratory and cardiovascular systems, but according to recent research, even in cognitive health, metabolic, and immune systems. The objective was to analyse the effect of long-term exposure to air pollution on selected immune system parameters, 8-isoprostane a parameter of oxidative stress, and alpha-1-antitrypsin a protease inhibitor.MethodsThe number of 381 probands aged 35–65 from two differently polluted regions was included. Lifetime exposures to PM10, PM2.5, NO2, B(a)P, and benzene for each proband were calculated based on historical pollutant concentrations observed. The selected blood parameters were analysed in relation to independent variables (air pollutants, socioeconomic factors, etc.) using multiple regression. Possible covariates were determined. In its end, the study was conceived as a case–control study, and the odds ratio was quantified, expressing the strength of the association of the monitored parameters with the region.ResultsThe average lifetime exposures to air pollution were significantly different between the two regions. Significant effects of the region were observed on IgM, IL-6, 8-isoprostane, and alpha-1-antitrypsin levels. The strongest positive association was observed between 8-isoprostane levels and benzene, PM2.5, PM10 and B(a)P. Odds ratio was 3.21 (95%CI 1.61–6.38). A significant negative association between all pollutants and IgM levels was observed even with covariate adjustment. Odds ratio was 1.80 (95%CI 1.15–2.82). A significant negative association between the alpha-1-antitrypsin levels and PM10, PM2.5, and benzene was found, independent of smoking as a covariate factor. Odds ratio was 1.77 (95%CI 1.09–2.87). In the case of IL-6, a significant effect of especially sleep as a covariate was observed. After covariates adjustment, a significant positive association between the IL-6 levels and PM10 and benzene was only observed. The odds ratio was 1.95 (95%CI 1.28–2.97).ConclusionsThe study confirmed that long-term exposure to air pollutants is associated with reduced levels of the protease inhibitor alpha-1-antitrypsin and decreased immune system performance by IgM. Furthermore, long-term exposure to air pollutants was associated with increased oxidative stress in humans, measured by 8-isoprostane levels. Residents who live in an industrial, environmentally polluted region showed elevated levels of IL-6.

Dietary Supplementation with n-3 Polyunsaturated Fatty Acids Delays the Phenotypic Manifestation of Krabbe Disease and Partially Restores Lipid Mediator Production in the Brain-Study in a Mouse Model of the Disease.

Lipid mediators from fatty acid oxidation have been shown to be associated with the severity of Krabbe disease (KD), a disorder linked to mutations in the galactosylceramidase (GALC) gene. This study aims to investigate the effects of n-3 polyunsaturated fatty acid (PUFA) supplementation on KD traits and fatty acid metabolism using Twitcher (Tw) animals as a natural model for KD. Wild-type (Wt), heterozygous (Ht), and affected Tw animals were treated orally with 36 mg n-3 PUFAs/kg body weight/day from 10 to 35 days of life. The end product of PUFA peroxidation (8-isoprostane), the lipid mediator involved in the resolution of inflammatory exudates (resolvin D1), and the total amount of n-3 PUFAs were analyzed in the brains of mice. In Tw mice, supplementation with n-3 PUFAs delayed the manifestation of disease symptoms (p < 0.0001), and in the bran, decreased 8-isoprostane amounts (p < 0.0001), increased resolvin D1 levels (p < 0.005) and increased quantity of total n-3 PUFAs (p < 0.05). Furthermore, total brain n-3 PUFA levels were associated with disease severity (r = -0.562, p = 0.0001), resolvin D1 (r = 0.712, p < 0.0001), and 8-isoprostane brain levels (r = -0.690, p < 0.0001). For the first time in a natural model of KD, brain levels of n-3 PUFAs are shown to determine disease severity and to be involved in the peroxidation of brain PUFAs as well as in the production of pro-resolving lipid mediators. It is also shown that dietary supplementation with n-3 PUFAs leads to a slowing of the phenotypic presentation of the disease and restoration of lipid mediator production.

Prediction of risks of comorbidity of type 2 diabetes mellitus and coronary heart disease taking into account plasma levels of 8-isoprostane and sirtuin-1

Prediction of risks of comorbidity of type 2 diabetes mellitus and coronary heart disease taking into account plasma levels of 8-isoprostane and sirtuin-1

Adverse effects of excessive dietary arachidonic acid on survival, PUFA-derived enzymatic and non-enzymatic oxylipins, stress response in rainbow trout fry

Arachidonic acid (C20: 4n-6, AA) plays a fundamental role in fish physiology, influencing growth, survival and stress resistance. However, imbalances in dietary AA can have detrimental effects on fish health and performance. Optimal AA requirements for rainbow trout have not been established. This study aimed to elucidate the effects of varying dietary AA levels on survival, growth, long-chain polyunsaturated fatty acid (LC-PUFA) biosynthetic capacity, oxylipin profiles, lipid peroxidation, and stress resistance of rainbow trout fry. Over a period of eight weeks, 4000 female rainbow trout fry at the resorptive stage (0.12 g) from their first feeding were fed diets with varying levels of AA (0.6%, 1.1% or 2.5% of total fatty acids) while survival and growth metrics were closely monitored. The dietary trial was followed by an acute confinement stress test. Notably, while the fatty acid profiles of the fish reflected dietary intake, those fed an AA-0.6% diet showed increased expression of elongase5, highlighting their inherent ability to produce LC-PUFAs from C18 PUFAs and suggesting potential AA or docosapentaenoic acidn-6 (DPAn-6) biosynthesis. However, even with this biosynthetic capacity, the trout fed reduced dietary AA had higher mortality rates. The diet had no effect on final weight (3.38 g on average for the three diets). Conversely, increased dietary AA enhanced eicosanoid production from AA, suggesting potential inflammatory and oxidative consequences. This was further evidenced by an increase in non-enzymatic lipid oxidation metabolites, particularly in the AA-2.5% diet group, which had higher levels of phytoprostanes and isoprostanes, markers of cellular oxidative damage. Importantly, the AA-1.1% diet proved to be particularly beneficial for stress resilience. This was evidenced by higher post-stress turnover rates of serotonin and dopamine, neurotransmitters central to the fish's stress response. In conclusion, a dietary AA intake of 1.1% of total fatty acids appears to promote overall resilience in rainbow trout fry.

A leaky gut contributes to postural imbalance in male patients with chronic obstructive pulmonary disease

AimsPatients with chronic obstructive pulmonary disease (COPD) frequently exhibit an inability to maintain postural balance. However, the contribution of increased intestinal permeability or leaky gut to the postural imbalance in COPD is not known. MethodsWe measured plasma zonulin, a marker of leaky gut, with relevance to postural balance in male controls (n = 70) and patients with mild (n = 67), moderate (n = 66), and severe (n = 58) COPD. We employed a short physical performance battery to evaluate postural balance in supine, tandem, and semi-tandem positions. We also measured handgrip strength (HGS), gait speed, plasma c-reactive proteins (CRP), and 8-isoprostanes as potential mechanistic connections between postural imbalance and leaky gut. ResultsCOPD patients demonstrated higher plasma zonulin, CRP, and 8-isoprostanes levels and lower balance, HGS, and gait speed than controls (all p < 0.05). These findings were more robust in patients with moderate and severe than mild COPD. In addition, plasma zonulin exhibited significant potential in diagnosing poor balance, low HGS, and gait speed in COPD patients (all p < 0.05). We also found significant correlations of plasma zonulin with CRP and 8-isoprostanes, providing heightened inflammation and oxidative stress as mechanistic connections between leaky gut and postural imbalance. ConclusionPlasma zonulin may be helpful in evaluating postural imbalance in COPD patients. Repairing intestinal leaks can be a therapeutic target to improve postural control in COPD.

Prenatal per- and polyfluoroalkyl substances (PFAS) and maternal oxidative stress: Evidence from the LIFECODES study

BackgroundPer- and polyfluoroalkyl substances (PFAS) are synthetic chemicals linked to adverse pregnancy outcomes. Although their underlying biological mechanisms are not fully understood, evidence suggests PFAS may disrupt endocrine functions and contribute to oxidative stress (OS) and inflammation. ObjectiveWe examined associations between early pregnancy PFAS exposure and OS biomarkers, exploring potential effect modifications by fetal sex and maternal race. MethodsWe used data from 469 LIFECODES participants with measured plasma PFAS (median 10 weeks gestation) and repeated measures (median 10, 18, 26, and 35 weeks gestation) of urinary OS biomarkers [8-iso-prostaglandin-F2α (8-isoprostane) and 8-hydroxydeoxyguanosine (8-OHdG)]. Protein damage biomarkers (chlorotyrosine, dityrosine, and nitrotyrosine) were additionally measured in plasma from a subset (N = 167) during the third visit. Associations between each PFAS and OS biomarkers were examined using linear mixed-effects models and multivariable linear regressions, adjusting for potential confounders, including maternal age, race, education level, pre-pregnancy BMI, insurance status, and parity. Effect modifications were evaluated by including an interaction term between each PFAS and fetal sex or maternal race in the models. ResultsWe observed significant positive associations between PFOS and 8-isoprostane, with a 9.68% increase in 8-isoprostane levels (95% CI: 0.10%, 20.18%) per interquartile range increase in PFOS. In contrast, PFUA was negatively associated [9.32% (95% CI: −17.68%, −0.11%)], while there were suggestive positive associations for MPAH and PFOA with 8-isoprostane. The associations of several PFAS with 8-OHdG varied by fetal sex, showing generally positive trends in women who delivered females, but negative or null in those who delivered males. No significant effect modification by maternal race was observed. ConclusionsThis study provides evidence linking PFAS exposure to OS during pregnancy, with potential sex-specific effects of certain PFAS on 8-OHdG. Further research should explore additional OS/inflammatory biomarkers and assess the modifying effects of dietary and behavioral patterns across diverse populations.

Evaluation of CSF 8-iso-prostaglandin F2α and erythrocyte anisocytosis as prognostic biomarkers for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Delayed cerebral ischemia (DCI) is a serious, life-threatening, complication affecting patients who have survived the initial bleeding from a ruptured intracranial aneurysm. Due to the challenging diagnosis, potential DCI prognostic markers should be of value in clinical practice. According to recent reports isoprostanes and red blood cell distribution (RDW) showed to be promising in this respect. We conducted a prospective study of 27 aSAH patients and control group (n = 8). All patients from the study group were treated within the first day of the initial bleeding. We collected data regarding clinical status and results of biochemical, and radiological examinations. We measured cerebrospinal fluid (CSF) concentration of 8-iso-prostaglandin F2α (F2-IsoP) and RDW on days 1, 3, and 5. Both CSF F2-IsoP level and RDW-SD measured on day 1 were significant predictors of DCI. The receiver operating characteristics curve for DCI prediction based on the multivariate model yielded an area under the curve of 0.924 (95% CI 0.824–1.000, p < 0.001). In our study, the model based on the combination of RDW and the level of isoprostanes in CSF on the first day after the initial bleeding showed a prognostic value for DCI prediction. Further studies are required to validate this observation.

Cigarette smoke-induced dysbiosis: comparative analysis of lung and intestinal microbiomes in COPD mice and patients

BackgroundThe impact of cigarette smoke (CS) on lung diseases and the role of microbiome dysbiosis in chronic obstructive pulmonary disease (COPD) have been previously reported; however, the relationships remain unclear.MethodsOur research examined the effects of 20-week cigarette smoke (CS) exposure on the lung and intestinal microbiomes in C57BL/6JNarl mice, alongside a comparison with COPD patients’ intestinal microbiome data from a public dataset.ResultsThe study found that CS exposure significantly decreased forced vital capacity (FVC), thickened airway walls, and induced emphysema. Increased lung damage was observed along with higher lung keratinocyte chemoattractant (KC) levels by CS exposure. Lung microbiome analysis revealed a rise in Actinobacteriota, while intestinal microbiome showed significant diversity changes, indicating dysbiosis. Principal coordinate analysis highlighted distinct intestinal microbiome compositions between control and CS-exposed groups. In the intestinal microbiome, notable decreases in Patescibacteria, Campilobacterota, Defferibacterota, Actinobacteriota, and Desulfobacterota were observed. We also identified correlations between lung function and dysbiosis in both lung and intestinal microbiomes. Lung interleukins, interferon-ɣ, KC, and 8-isoprostane levels were linked to lung microbiome dysbiosis. Notably, dysbiosis patterns in CS-exposed mice were similar to those in COPD patients, particularly of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 patients. This suggests a systemic impact of CS exposure.ConclusionIn summary, CS exposure induces significant dysbiosis in lung and intestinal microbiomes, correlating with lung function decline and injury. These results align with changes in COPD patients, underscoring the important role of microbiome in smoke-related lung diseases.