F2-isoprostane Concentrations Research Articles

A phase II randomized, double-blind, placebo-controlled study of Nuvastatic (C50SEW505OESA), a standardized rosmarinic acid-rich polymolecular botanical extract formulation to reduce cancer-related fatigue in patients with solid tumors.

We evaluated the efficacy and safety of Nuvastatic™ (C5OSEW5050ESA)in improving cancer-related fatigue (CRF) among cancer patients. This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II-IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000mg (N = 56) or placebo (N = 54) thrice daily for 9weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA). The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic™ group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p < 0.001, partial η2 = 0.333). The Nuvastatic™ group significantly reduced VAS-F fatigue (F (2, 210) = 9.534, p < 0.001, partial η2 = 0.083), improved quality of life (QoL) (F (1.2, 127.48) = 34.07, p < 0.001, partial η2 = 0.243), and lowered urinary F2-IsoP concentrations (mean difference (95% CI) = 55.57 (24.84, 86.30)), t (55) = 3.624, p < 0.001, Cohen's d (95% CI) = 0.48 (0.20, 0.75)). Reported adverse events were vomiting (0.9%), fever (5.4%), and headache (2.7%). Nuvastatic™ is potentially an effective adjuvant for CRF management in solid tumor patients and worthy of further investigation in larger trials. ClinicalTrial.gov ID: NCT04546607. Study registration date (first submitted): 11-05-2020.

The severity of COVID-19 upon hospital admission is associated with plasma omega-3 fatty acids

Fatty acids are precursors of inflammatory oxylipins. In the context of COVID-19, an excessive production of pro-inflammatory cytokines is associated with disease severity. The objective was to investigate whether the baseline omega 3/omega 6 fatty acids ratio and the oxylipins were associated with inflammation and oxidative stress in unvaccinated patients with COVID-19, classified according to the severity of the disease during hospitalization. This Prospective population-based cohort study included 180 hospitalized patients with COVID-19. The patients were classified into five groups according to the severity of their disease. Group 1 was the least severe and Group 5 was the most severe. Three specific types of fatty acids—eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA)—as well as their enzymatic and non-enzymatic oxylipins were determined using chromatography coupled mass spectrometry. There was no difference in the ratio of omega-3 to omega-6 fatty acids between the groups (p = 0.276). However, the EPA/AA ratio was lower in Group 4 compared to Group 1 (p = 0.015). This finding was associated with an increase in both C-Reactive Protein (p < 0.001) and Interleukin-6 (p = 0.002). Furthermore, the concentration of F2-Isoprostanes was higher in Group 4 than in Group 1 (p = 0.009), while no significant changes were observed for other oxylipins among groups. Multivariate analysis did not present any standard of biomarkers, suggesting the high complexity of factors involved in the disease severity. Our hypothesis was confirmed in terms of EPA/AA ratio. A higher EPA/AA ratio upon hospital admission was found to be associated with lower concentration of C-Reactive Protein and Interleukin-6, leading to a better prognosis of hospitalized SARS-CoV-2 patients. Importantly, this beneficial outcome was achieved without any form of supplementation. The trial also provides important information that can be further applied to reduce the severity of infections associated with an uncontrolled synthesis of pro-inflammatory cytokines.Trial registration: https://clinicaltrials.gov/study/NCT04449718—01/06/2020. ClinicalTrials.gov Identifier: NCT04449718.

Loss of flavin-containing monooxygenase 3 modulates dioxin-like polychlorinated biphenyl 126-induced oxidative stress and hepatotoxicity

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.

Temperature stability of urinary F2-isoprostane and 8-hydroxy-2′-deoxyguanosine

BackgroundClinical and epidemiological studies employ long-term temperature storage but the effect of temperature on the stability of oxidative stress (OS) markers is unknown. We investigated the effects of storage at −20 °C and −80 °C over 4–9 months on F2-isoprostanes (F2-IsoP) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in urine of children, a population group among whom the measurement of these markers is still limited. MethodsPaired spot urine samples from 87 children aged 8.9–16.9 years (52.9% boys) were analyzed. Samples were preserved with 0.005% (w/v) butylated hydroxytoluene, portioned and stored within 2.5 h (median) of collection. Samples were analyzed in duplicate or triplicate using commercial ELISA kits and their correlations were evaluated. ResultsF2-IsoP and 8-OHdG showed high correlations (Spearman rho of 0.90 and 0.97, respectively; P < 0.0001) with storage at −20 °C and −80 °C. There was a strong agreement among categories of values for F2-IsoP (Kappa = 0.76 ± 0.08, agreement = 83.9%, P < 0.0001) and 8-OHdG: (Kappa = 0.83 ± 0.08, agreement = 88.4%, P < 0.0001). The correlation between the temperatures for F2-IsoP concentrations was also high when stored for <4 (0.93), 4 (0.93), and 5 months (0.88), all P < 0.0001. For 8-OHdG, Spearman correlations at <8, 8, and 9 months of storage at −20 °C and −80 °C were 0.95, 0.98, and 0.96 (all P < 0.0001), respectively. ConclusionsUrine storage with BHT for up to nine months at a temperature of −20 °C to −80 °C yields highly comparable concentrations of F2-IsoP and 8-OHdG.

Profile of F2-Isoprostane Level After 5-Day Administration of Robusta Coffee at a Steady State Dose in Subjects Performing Physical Exercise

This study aims to analyze the effect of robusta Dampit coffee on F2-isoprostane levels influenced by ROS due to excessive exercise. This study was an experimental study with a pre- and post-test control group design with coffee administration. The total sample was 18 untrained or sedentary male, divided into two groups: coffee group (COF, n=9) and control/placebo group (PLB, n=9). The COF group was given 2 cups of filtered coffee a day (100 ml/cup) at 12-hour intervals for 5 days. Both groups performed physical exercise with a step test on day 6. Blood samples were collected pre and two hours post exercise. F2-isoprostane concentration was analyzed using the F2-isoprostane biomarker and ELISA to measure the level of lipid peroxidation. Results showed a decrease in F2-isoprostane levels in both COF (pre: 1531.57±278.13 pg/mL; post: 1367.6±230.24 pg/mL; p=0.110) and PLB (pre: 1716.65±501.19 pg/mL; post: 1600.02±500.59 pg/mL; p=0.139) groups with a greater decrease in the COF group. However, this reduction was not significantly different between groups (p=0.734). Although not significantly different, exercising participants tended to have lower F2-isoprostane levels after consuming robusta coffee for five days at a steady state dose. Therefore, further investigation is needed to ascertain the physiological consequences of coffee administration over a longer period of time and its effect on recovery speed. Keywords: coffee, exercise, lipid peroxidation, and F2-isoprostane

Antioxidant enzyme and DNA base repair genetic risk scores' associations with systemic oxidative stress biomarker in pooled cross-sectional studies.

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.

Green tea extract supplementation does not modify plasma concentration of F2-isoprostanes in women who are postmenopause: Findings from a randomized controlled trial

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.

Critically ill septic patients have elevated oxidative stress biomarkers: lack of attenuation by parenteral vitamin C

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).

Supplementation of Red Fruit (Pandanus Conoideus) Extract Improved Lipid Profile, Decreased Concentration of F2 Isoprostane and Bodyweight in Male Wistar Strain (Rattus Norvegicus) Rats Given High-Fat Diet

Backgrounds: Red fruit plant (Pandanus conoideus) that grows in eastern Indonesia, has the strong antioxidant properties, such as flavonoids, tannins, beta-carotene, vitamin C, and vitamin E. Study objectives to prove the antioxidant effect of red fruit extract inhibit dyslipidemia, the F2 Isoprostane concentration, the weight gain in animal with high lipid diet. Methods: The pre and posttest control group design experiment study was conducted on male Wistar rats. The subject was divided randomly into two groups. Both groups were administrated with hegh fat diet. The control group was blinded with 1 mL aquadestylates, and the treatment group, which was treated with 168 mg red fruit extract in 1 mL for 30 days. Dependent variables; lipid profile, levels of F2 isoprostane, and bodyweight were measured before and after intervention. Results: We found the improvement of lipid profile in the treatment group; decreased of LDL cholesterol (p&lt;0.001), triglycerides (p&lt;0.001), total cholesterol (p&lt;0.001), and increased HDL cholesterol (p&lt;0.001). Other wised there was no change of lipid profile in the control group. F2 Isoprostane was also decreased (p&lt;0.001) in the treatment group, but not in the control group. The bodyweight was decreased in the treatment goup (p&lt;0.001), but in contrary increased in the control group (p&lt;0.001). Conclusion: Supplementation of red fruit extract (Pandanus conoideus) significantly improved the lipid profile, decreased levels of F2 isoprostane, as well as bodyweight on male Wistar strain (Rattus norvegicus) rats that was administrated with a high-fat diet Keywords: antioxidant, red fruit extract, lipid profile, F2 Isoprostane, body weight

The association between prenatal F2-isoprostanes and child wheeze/asthma and modification by maternal race

BackgroundChildhood 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. MethodsWe 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. ResultsThe 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. ConclusionPrenatal 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.

Effect of Green Tea Extract Supplementation and Impact of Catechol-O-Methyltransferase Genotype on Plasma Concentration of F2-Isoprostanes in Women Who Are Post-menopause

ObjectivesGreen tea extract (GTE) is a potential mitigator of oxidative stress. F2-isoprostanes are a reliable and easily measured marker of oxidative stress. Genetic polymorphisms in the catechol-o-methyltransferase (COMT) gene may modify green tea catechin metabolism and potentially prolong exposure to catechins in those with lower activity COMT genotypes. The objective of this study was to assess if GTE supplementation would result in a decrease in plasma F2-isoprostanes concentration as compared to placebo. A secondary objective was to determine the impact of the COMT genotype on F2-isoprostanes concentration among participants receiving GTE. MethodsThis study is a secondary analysis of the Minnesota Green Tea Trial (MGTT), a randomized placebo-controlled, double-blinded trial investigating the effects of GTE in nearly 1000 women who were generally healthy and post-menopause. The treatment group consumed 843 mg of epigallocatechin gallate daily for 12 months as two capsules twice daily, vs identically appearing placebo capsules for controls. The current analysis was conducted using data from the 254 participants who had plasma F2-isoprostanes analyzed by a validated gas chromatography-mass spectrometry method. ResultsThe mean values of age and BMI were 59.7 years and 25.1 kg/m2, respectively, and more than 96% of the women were non-Hispanic white. Using ANCOVA model adjusting for dietary protein intake there was no statistically significant difference in plasma F2-isoprostanes concentrations between participants in the GTE (n = 133) as compared with the placebo group (n = 125) after 12 months (P = 0.557). There were no significant interactions between treatment and age, or BMI, physical activity, smoking history and alcohol intake. Additionally, COMT genotype did not modify the effect of GTE supplementation on F2-isoprostanes concentration in those who consumed GTE supplement (P = 0.603). ConclusionsAmong participants in the MGTT who were 50–70 years old and post-menopause, consuming GTE supplements daily for one year did not result in a significant decrease in plasma F2-isoprostanes concentration, a biomarker of oxidative stress. Likewise, COMT genotype did not modify the effect of GTE supplementation on F2-isoprostanes concentration. Funding SourcesNIH/NCI (Grant R01 CA127236).

Severe Glutathione Deficiency, Oxidative Stress and Oxidant Damage in Adults Hospitalized with COVID-19: Implications for GlyNAC (Glycine and N-Acetylcysteine) Supplementation.

Humanity is battling a respiratory pandemic pneumonia named COVID-19 which has resulted in millions of hospitalizations and deaths. COVID-19 exacerbations occur in waves that continually challenge healthcare systems globally. Therefore, there is an urgent need to understand all mechanisms by which COVID-19 results in health deterioration to facilitate the development of protective strategies. Oxidative stress (OxS) is a harmful condition caused by excess reactive-oxygen species (ROS) and is normally neutralized by antioxidants among which Glutathione (GSH) is the most abundant. GSH deficiency results in amplified OxS due to compromised antioxidant defenses. Because little is known about GSH or OxS in COVID-19 infection, we measured GSH, TBARS (a marker of OxS) and F2-isoprostane (marker of oxidant damage) concentrations in 60 adult patients hospitalized with COVID-19. Compared to uninfected controls, COVID-19 patients of all age groups had severe GSH deficiency, increased OxS and elevated oxidant damage which worsened with advancing age. These defects were also present in younger age groups, where they do not normally occur. Because GlyNAC (combination of glycine and N-acetylcysteine) supplementation has been shown in clinical trials to rapidly improve GSH deficiency, OxS and oxidant damage, GlyNAC supplementation has implications for combating these defects in COVID-19 infected patients and warrants urgent investigation.

Associations of dietary, lifestyle, other participant characteristics, and oxidative balance scores with plasma F2-isoprostanes concentrations in a pooled cross-sectional study.

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. 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. 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). Multiple dietary and lifestyle characteristics, individually, and especially collectively, may contribute to systemic oxidative stress.

A randomised controlled trial of succinylated gelatin (4%) fluid on urinary acute kidney injury biomarkers in cardiac surgical patients

BackgroundFluid resuscitation is frequently required for cardiac surgical patients admitted to the intensive care unit. The ideal fluid of choice in regard to efficacy and safety remains uncertain. Compared with crystalloid fluid, colloid fluid may result in less positive fluid balance. However, some synthetic colloids are associated with increased risk of acute kidney injury (AKI). This study compared the effects of succinylated gelatin (4%) (GEL) with compound sodium lactate (CSL) on urinary AKI biomarkers in patients after cardiac surgery.MethodsCardiac surgical patients who required an intravenous fluid bolus of at least 500 mL postoperatively were randomly allocated to receive GEL or CSL as the resuscitation fluid of choice for the subsequent 24 h. Primary outcomes were serial urinary neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C concentrations measured at baseline, 1 h, 5 h and 24 h after enrolment, with higher concentrations indicating greater kidney injury. Secondary biomarker outcomes included urinary clusterin, α1-microglobulin and F2-isoprostanes concentrations. Differences in change of biomarker concentration between the two groups over time were compared with mixed-effects regression models. Statistical significance was set at P < 0.05.ResultsForty cardiac surgical patients (n = 20 per group) with similar baseline characteristics were included. There was no significant difference in the median volume of fluid boluses administered over 24 h between the GEL (1250 mL, Q1–Q3 500–1750) and CSL group (1000 mL, Q1–Q3 500–1375) (P = 0.42). There was a significantly greater increase in urinary cystatin C (P < 0.001), clusterin (P < 0.001), α1-microglobulin (P < 0.001) and F2-isoprostanes (P = 0.020) concentrations over time in the GEL group, compared to the CSL group. Change in urinary NGAL concentration (P = 0.68) over time was not significantly different between the groups. The results were not modified by adjustment for either urinary osmolality or EuroSCORE II predicted risk of mortality.ConclusionsThis preliminary randomised controlled trial showed that use of succinylated gelatin (4%) for fluid resuscitation after cardiac surgery was associated with increased biomarker concentrations of renal tubular injury and dysfunction, compared to crystalloid fluid. These results generate concern that use of intravenous gelatin fluid may contribute to clinically relevant postoperative AKI.Trial registration ANZCTR.org.au, ACTRN12617001461381. Registered on 16th October, 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373619&isReview=true.

Biomarkers representing key aging-related biological pathways are associated with subclinical atherosclerosis and all-cause mortality: The Framingham Study.

Increased oxidative stress, leukocyte telomere length (LTL) shortening, endothelial dysfunction, and lower insulin-like growth factor (IGF)-1 concentrations reflect key molecular mechanisms of aging. We hypothesized that biomarkers representing these pathways are associated with measures of subclinical atherosclerosis and all-cause mortality. We evaluated up to 2,314 Framingham Offspring Study participants (mean age 61 years, 55% women) with available biomarkers of aging: LTL, circulating concentrations of IGF-1, asymmetrical dimethylarginine (ADMA), and urinary F2-Isoprostanes indexed to urinary creatinine. We evaluated the association of each biomarker with coronary artery calcium [ln (CAC+1)] and carotid intima-media thickness (IMT). In multivariable-adjusted linear regression models, higher ADMA levels were associated with higher CAC values (βADMA per 1-SD increase 0.25; 95% confidence interval [CI] [0.11, 0.39]). Additionally, shorter LTL and lower IGF-1 values were associated with higher IMT values (βLTL -0.08, 95%CI -0.14, -0.02, and βIGF-1 -0.04, 95%CI -0.08, -0.01, respectively). During a median follow-up of 15.5 years, 593 subjects died. In multivariable-adjusted Cox regression models, LTL and IGF-1 values were inversely associated with all-cause mortality (hazard ratios [HR] per SD increase in biomarker, 0.85, 95% CI 0.74-0.99, and 0.90, 95% CI 0.82-0.98 for LTL and IGF-1, respectively). F2-Isoprostanes and ADMA values were positively associated with all-cause mortality (HR per SD increase in biomarker, 1.15, 95% CI, 1.10-1.22, and 1.10, 95% CI, 1.02-1.20, respectively). In our prospective community-based study, aging-related biomarkers were associated with measures of subclinical atherosclerosis cross-sectionally and with all-cause mortality prospectively, supporting the concept that these biomarkers may reflect the aging process in community-dwelling adults.

Serum Cotinine, Serum F2-isoprostane and Risk of Metabolic Syndrome in Adult Male Tobacco Users

Data on risk of metabolic syndrome among various forms of tobacco consumption in Myanmar tobacco users are currently limited. The present study aimed to determine and compare nicotine metabolites serum cotinine, oxidative stress marker serum F2-isoprostane in adult male tobacco users, and to find out relationships between these parameters and risk of metabolic syndrome. This cross-sectional study was done in 30 to 45 years old males: 84 cigarette smokers, 84 cheroot smokers and 84 betel quid with tobacco chewers. Metabolic syndrome was defined by National Cholesterol Education Program Adult Treatment Panel III definition. Serum cotinine concentration of cigarette smokers was significantly higher than that of cheroot smokers (p=0.026), however, no significant difference was seen between cigarette smokers and betel quid with tobacco chewers (p=1.000), and between cheroot smokers and betel quid with tobacco chewers (p=0.248). Serum F2-isoprostane concentration was significantly higher (p=0.001) in cigarette smokers than cheroot smokers and betel quid with tobacco chewers, but no significant difference was observed between cheroot smokers and betel quid with tobacco chewers (p=1.000). Compared with betel quid with tobacco chewers, cigarette smokers had 5.2 times (95% CI, 2.3-11.4) (p&lt;0.001) and cheroot smokers had 1.4 times (95% CI, 0.62-3.3) (p=0.402) higher risk of having metabolic syndrome. There was a significant association between the presence of metabolic syndrome and high serum cotinine as well as high serum F2-isoprostane. A significant correlation between serum cotinine and serum F2-isoprostane was found in betel quid with tobacco chewers, but not in cigarette smokers and cheroot smokers. The present study showed that both nicotine and oxidative stress take part in the pathogenesis of metabolic syndrome. Cigarette smoking has the highest risk of having metabolic syndrome, however, cheroot smoking as well as betel quid with tobacco chewing is related to metabolic syndrome as well.

The Role of Urine F2-ISOPROSTANE CONcentration in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Haemorrhage-A Poor Prognostic Factor.

Background: The pathophysiology of delayed cerebral ischemia (DCI) remains unclear. One of the hypotheses suggests that reactive oxygen species play a role in its onset. Thus, we studied F2-isoprostanes (F2-IsoPs)—oxidative stress biomarkers. Our goal was to improve the early diagnosis of DCI in a non-invasive way. Methods: We conducted a prospective single center analysis of 38 aneurysmal subarachnoid hemorrhage patients. We assessed urine F2-IsoP concentration using immunoenzymatic arrays between the first and fifth day after bleeding. A correlation between urine F2-IsoP concentration and DCI occurrence was examined regarding clinical conditions and outcomes. Results: The urine F2-IsoP concentrations were greater than those in the control groups (p < 0.001). The 3rd day urine F2-IsoPs concentrations were correlated with DCI occurrence (p < 0.001) and long term outcomes after 12 months (p < 0.001). Conclusions: High levels of urine F2-IsoPs on day 3 can herald DCI.

Feline urinary F2-isoprostanes measured by enzyme-linked immunoassay and gas chromatography-mass spectroscopy are poorly correlated.

15-F2T-isoprostanes are byproducts of lipid peroxidation and were determined to be the best marker of oxidative injury in a rodent model of oxidative stress. A previous study compared methods for measurement of urinary F2-isoprostanes (gas chromatography and negative ion chemical ionization-mass spectrometry, GC-NICI-MS; and ELISA) and found poor agreement in dogs, horses, and cows. Surprisingly, fair agreement between these methods was identified in a small population of cats. We evaluated the agreement between GC-NICI-MS and ELISA of urinary F2-isoprostanes in the urine of 50 mature cats ranging from healthy to systemically ill. All urine samples had detectable levels of F2-isoprostanes by both methods. Significant proportional bias and poor agreement were identified between the 2 methods (ρ = 0.364, p = 0.009) for all cats, and in subgroup analysis based on health status. The concentration of urinary F2-isoprostanes was significantly lower in systemically ill cats compared to healthy cats when measured by ELISA (p = 0.002) but not by GC-NICI-MS (p = 0.068). Our results indicate that GC-NICI-MS and ELISA have poor agreement when measuring urinary F2-isoprostanes in cats.

Intraoperative Oxidative Damage and Delirium after Cardiac Surgery.

Mechanisms of postoperative delirium remain poorly understood, limiting development of effective treatments. We tested the hypothesis that intraoperative oxidative damage is associated with delirium and neuronal injury and that disruption of the blood-brain barrier modifies these associations. In a prespecified cohort study of 400 cardiac surgery patients enrolled in a clinical trial of atorvastatin to reduce kidney injury and delirium, we measured plasma concentrations of F2-isoprostanes and isofurans using gas chromatography-mass spectrometry to quantify oxidative damage, ubiquitin carboxyl-terminal hydrolase isozyme L1 to quantify neuronal injury, and S100 calcium-binding protein B using enzyme-linked immunosorbent assays to quantify blood-brain barrier disruption before, during, and after surgery. We performed the Confusion Assessment Method for the Intensive Care Unit twice daily to diagnose delirium. We measured the independent associations between intraoperative F2-isoprostanes and isofurans and delirium (primary outcome) and postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (secondary outcome), and we assessed if S100 calcium-binding protein B modified these associations. Delirium occurred in 109 of 400 (27.3%) patients for a median (10th, 90th percentile) of 1.0 (0.5, 3.0) days. In the total cohort, plasma ubiquitin carboxyl-terminal hydrolase isozyme L1 concentration was 6.3 ng/ml (2.7, 14.9) at baseline and 12.4 ng/ml (7.9, 31.2) on postoperative day 1. F2-isoprostanes and isofurans increased throughout surgery, and the log-transformed sum of intraoperative F2-isoprostanes and isofurans was independently associated with increased odds of postoperative delirium (odds ratio, 3.70 [95% CI, 1.41 to 9.70]; P = 0.008) and with increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (ratio of geometric means, 1.42 [1.11 to 1.81]; P = 0.005). The association between increased intraoperative F2-isoprostanes and isofurans and increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 was amplified in patients with elevated S100 calcium-binding protein B (P = 0.049). Intraoperative oxidative damage was associated with increased postoperative delirium and neuronal injury, and the association between oxidative damage and neuronal injury was stronger among patients with increased blood-brain barrier disruption.

Oxidant stress and renal function among children with chronic kidney disease: a repeated measures study

It is hypothesized that chronic kidney disease (CKD) induces oxidant stress which contributes to the decline in kidney function. However, few studies have incorporated longitudinal designs and no studies have investigated this association among children. Using data from the Chronic Kidney Disease in Children (CKiD) study, we examined longitudinal associations between urinary biomarkers of oxidant stress, 8-OH deoxyguanosine (8-OHdG) and F2-isoprostane, and measures of renal function and blood pressure among children with CKD. Baseline levels of 8-OHdG were positively associated with estimated glomerular filtration rate (eGFR) over time and a log-unit increase in baseline 8-OHdG predicted a 5.68 ml/min/1.73 m2 increase in eGFR (95% Confidence Interval (CI): 3.75, 7.61). This association was attenuated when longitudinal measures of 8-OHdG were analyzed in relation to longitudinal eGFR (per log-unit increase in 8-OHdG, β = 0.81, 95% CI: 0.22, 1.39). Baseline 8-OHdG concentrations were also associated with decreased proteinuria over time, as measured by urinary protein:creatinine ratio. In addition, F2-isoprostane concentrations were associated with increases in eGFR, but only when baseline levels (vs. longitudinal levels) were considered in relation to longitudinal eGFR. There were no significant associations between either 8-OHdG or F2-isoprostane and blood pressure over time. Urinary measures of oxidant stress are not associated with worsening GFR over time. Our findings suggest that excretion of these biomarkers may be influenced by changes in glomerular and tubular function in varying patterns, which would limit their value in evaluating the impact of oxidant stress on CKD progression in children.