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

BACKGROUND: Per- 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. OBJECTIVE: We examined associations between early pregnancy PFAS exposure and OS biomarkers, exploring potential effect modifications by fetal sex and maternal race. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: This 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.

DNA damage in inhabitants exposed to heavy metals near Hudiara drain, Lahore, Pakistan.

The current study was conducted on the inhabitants living in the area adjacent to the Hudiara drain using bore water and vegetables adjacent to the Hudiara drain. Toxic heavy metals badly affect human health because of industrial environmental contamination. Particularly hundreds of millions of individuals globally have faced the consequences of consuming water and food tainted with pollutants. Concentrations of heavy metals in human blood were elevated in Hudiara drainings in Lahore city, Pakistan, due to highly polluted industrial effluents. The study determined the health effects of high levels of heavy metals (Cd, Cu, Zn, Fe, Pb, Ni, Hg, Cr) on residents of the Hudiara draining area, including serum MDA, 8-Isoprostane, 8-hydroxyguanosine, and creatinine levels. An absorption spectrophotometer was used to determine heavy metals in wate water, drinking water, soil, plants and human beings blood sampleas and ELISA kits were used to assess the level of 8-hydroxyguanosine, MDA, 8-Isoprostane in plasma serum creatinine level. Waste water samples, irrigation water samples, drinking water samples, Soil samples, Plants samples and blood specimens of adult of different weights and ages were collected from the polluted area of the Hudiara drain (Laloo and Mohanwal), and control samples were obtained from the unpolluted site Sheiikhpura, 60 km away from the site. Toxic heavy metals in blood damage the cell membrane and DNA structures, increasing the 8-hydroxyguanosine, MDA, creatinine, and 8-Isoprostane. Toxic metals contaminated bore water and vegetables, resulting in increased levels of creatinine, MDA, Isoprostane, and 8-hydroxy-2-guanosine in the blood of inhabitants from the adjacent area Hudiara drain compared to the control group. In addition,. This study also investigated heavy metal concentrations in meat and milk samples from buffaloes, cows, and goats. In meat, cow samples showed the highest Cd, Cu, Fe and Mn concentrations. In milk also, cows exhibited elevated Cu and Fe levels compared to goats. The results highlight species-specific variations in heavy metal accumulation, emphasizing the need for targeted monitoring to address potential health risks. The significant difference between the two groups i.e., the control group and the affected group, in all traits of the respondents (weight, age, heavy metal values MDA, 8-Isoprostane, 8-hydroxyguaniosine, and serum creatinine level). Pearson's correlation coefficient was calculated. The study has shown that the level of serum MDA, 8-Isoprostane, 8-hydroxyguaniosine, or creatinine has not significantly correlated with age, so it is independent of age. This study has proved that in Pakistan, the selected area of Lahore in the villages of Laloo and Mohanwal, excess of heavy metals in the human body damages the DNA and increases the level of 8-Isoprostane, MDA, creatinine, and 8-hydroxyguaniosine. As a result, National and international cooperation must take major steps to control exposure to heavy metals.

Effects of Date Palm Pollen Supplementations on The Expression of PRDX1 and PRDX6 Genes in Infertile Men: A Controlled Clinical Trial.

BACKGROUND: Accumulating evidences suggest that date palm pollen (DPP) induces antioxidant activity and improves semen parameters in male rats. However, there is a few scientific evidences in support of the DPP effects on human male fertility. Hence, the effect of oral consumption of DPP on sperm parameters and expression pattern of Peroxiredoxin- 1 (PRDX1) and Peroxiredoxin-6 (PRDX6) genes was evaluated in men with infertility. MATERIALS AND METHODS: The current controlled clinical trial included 40 men with infertility (DPP group) and 10 normospermic fertile men as controls. The DPP group received gelatinous capsules of DPP (400 mg/kg) for 74 days. Semen sampling was done before and after treatment in the both groups. Semen analysis and 8-isoprostane concentration assessments were performed by computer-assisted sperm analysis and ELISA methods, respectively. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were employed to explore expression of PRDX1 and PRDX6 genes. RESULTS: DPP consumption significantly improved semen volume (P=0.030), count (P<0.001) and morphology of sperm (P=0.023). Concentration of 8-isoprostane was significantly decreased after intervention in the DPP group (P<0.001). DPP consumption led to a significant elevation in the expression of PRDX1 and PRDX6 genes (P<0.001). Elevated gene expression of PRDX6 and PRDX1 was positively correlated with improved parameters of sperm including count, volume, motility and morphology. CONCLUSION: Taken together, DPP seems to promote sperm quality through a decrease in reactive oxygen species (ROS) by increasing expression of antioxidant genes. Further large-scale studies are required to challenge this hypothesis (registration number: IRCT2015021221014N2).

Room air versus 100% oxygen for delivery room resuscitation of preterm neonates in low resource settings: A randomised, blinded, controlled trial.

AIM: International Liaison Committee on Resuscitation (ILCOR-2020) report recommend starting delivery room resuscitation of all preterm neonates of <35 weeks' gestation with 21-30% oxygen. However, the correct initial oxygen concentration for resuscitation of preterm neonates in delivery room is inconclusive. In this blinded, randomised, controlled trial, we compared room air with 100% oxygen for oxidative stress and clinical outcomes in delivery room resuscitation of preterm neonates. METHODS: Preterm neonates 28-33 weeks' gestation requiring positive pressure ventilation at birth were randomly allocated to room air or 100% oxygen. Investigators, outcome assessors and data analysts were blinded. Rescue 100% oxygen was used whenever trial gas failed (need for positive pressure ventilation >60 s or chest compression). PRIMARY OUTCOME: Plasma 8-isoprostane levels at 4 h of age. SECONDARY OUTCOMES: mortality by discharge, bronchopulmonary dysplasia, retinopathy of prematurity and neurological status at 40 weeks post-menstrual age. All subjects were followed till discharge. Intention to treat analysis was carried out. RESULTS: A total of 124 neonates were randomised to room air (n = 59) or 100% oxygen (n = 65). Isoprostane level at 4 h was similar in both the groups (median (interquartile range): 280 (180-430) vs. 250 (173-360) pg/mL, P = 0.47). No difference was observed in mortality and other clinical outcomes. Room air group had higher treatment failures (27 (46%) vs. 16 (25%); relative risk (RR) 1.9 (1.1-3.1)) and took longer time to establish regular respiration (230 ± 231 vs. 182 ± 261, mean difference = 48 (40, 136) seconds). CONCLUSIONS: In preterm neonates 28-33 weeks' gestation requiring resuscitation in the delivery room, room air (21%) is not the correct concentration to initiate resuscitation. Larger controlled trials involving multiple centres in low- and middle-income countries are immediately required for a conclusive answer.

Impact of modernization on oxidative stress among indigenous populations in northern Laos.

OBJECTIVES: To explore the impact of modernization on oxidative stress during a momentous health transition process, we investigated differences in oxidative stress among the indigenous populations of villages in northern Laos with different levels of modernization. METHODS: We conducted a cross-sectional study of 380 adults in three villages with different levels of modernization. Three biomarkers related to oxidative stress were measured: urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane concentrations (both measured by liquid chromatography-tandem mass spectrometry), and blood telomere length (measured with qPCR). We examined associations between village-level modernization and oxidative stress-related biomarkers in a multilevel analysis including a random effect and covariates. RESULTS: The geometric means of urinary 8-OHdG and 8-isoprostane concentrations were 2.92 and 0.700 µg/g creatinine, respectively, in our study population. Higher urinary 8-OHdG concentrations and shorter telomeres were observed in participants from the more modernized villages, whereas urinary 8-isoprostane concentrations did not differ significantly among villages. CONCLUSIONS: Our findings imply that modernization-induced changes in lifestyle may increase oxidative DNA damage. Baseline levels of oxidative lipid damage are expected to be high in the indigenous populations of northern Laos. Assessments of oxidative stress may provide valuable insights into the mechanisms of health transition in specific populations.

The effects of exercise and diet on oxidative stress and telomere length in breast cancer survivors.

PURPOSE: Cancer and its treatments accelerate biological aging. This analysis tested the hypothesis that exercise and diet reduce oxidative stress and prevent telomere shortening in breast cancer survivors. METHODS: In a 2 × 2 factorial design, 342 breast cancer survivors who were insufficiently physically active and had overweight or obesity at enrollment were randomized to one of four treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. The endpoints of this analysis were the change from baseline to week 52 in 8-iso-prostaglandin F2α (8-iso-PGF2α) and lymphocyte telomere length. RESULTS: Baseline telomere length was shorter than age-adjusted normative values (median difference: - 1.8 kilobases; 95% CI - 2.4, - 1.1); equivalent to 21 years (95% CI 17, 25) of accelerated chronological aging. Compared to control, exercise alone did not change 8-iso-PGF2α [9.9%; 95% confidence interval (CI) - 1.0, 20.8] or telomere length (13.8%; 95% CI - 15.6, 43.3). Compared to control, diet alone was associated with reduced 8-iso-PGF2α (- 10.5%; 95% CI - 19.5, - 1.5) but did not change telomere length (12.1%; 95% CI - 17.2, 41.3). Compared to control, exercise plus diet was associated with reduced 8-iso-PGF2α (- 9.8%; 95% CI - 18.7, - 0.9) but did not change telomere length (- 8.5%; 95% CI - 32.1, 15.2). Change in 8-iso-PGF2α did not correlate with change in telomere length (r = 0.07; 95% CI - 0.07, 0.20). CONCLUSION: In breast cancer survivors, diet alone or exercise plus diet were associated with reduced oxidative stress but did not change telomere length. This analysis may inform future trials that aim to optimize healthy aging in cancer survivors.

Oxidative Stress and Cardiovascular Risk Factors: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Introduction-Oxidative stress is linked to cardiovascular diseases (CVD) and is suggested to vary by sex. However, few population-level studies have explored these associations and the majority comprise populations with advanced CVD. We assessed urinary isoprostane concentrations, a standard measure of oxidative stress, in a relatively young and healthy cohort, hypothesizing that higher oxidative stress is associated with an adverse cardiometabolic profile and female sex. Methods-Oxidative stress was measured in 475 women and 266 men, aged 48-55 years, from the Coronary Artery Risk Development in Young Adults (CARDIA) study using urinary 8-isoprostane (IsoP) and 2,3-dinor-8-isoprostane (IsoP-M). Multivariable-adjusted regression was used to evaluate cross-sectional associations. As secondary analysis, previously measured plasma F2-isoprostanes (plasma IsoP) from another CARDIA subset was similarly analyzed. Results-Mean (SD) ages for men and women were 52.1(2.3) and 52.2(2.2) years, respectively (p = 0.46), and 39% of the participants self-identified as Black (vs. White). Before adjustments, female sex was associated with higher median urinary IsoP (880 vs. 704 ng/g creatinine in men; p < 0.01) and IsoP m (1675 vs. 1284 ng/g creatinine in men; p < 0.01). Higher body mass index (BMI), high-density cholesterol (HDL-C), and triglycerides, current smoking, and less physical activity were associated with higher oxidative stress. Diabetes was not associated with urinary IsoP but was associated with lower IsoP m and plasma IsoP. Higher serum creatinine showed diverging associations with higher plasma and lower urinary isoprostane concentrations. Conclusions-Different isoprostane entities exhibit varying association patterns with CVD risk factors, and therefore are complementary, rather than interchangeable, in assessment of oxidative stress. Still, consistently higher isoprostanes among women, smokers, less active persons, and those with higher BMI and plasma triglycerides could reflect higher oxidative stress among these groups. While urinary isoprostanes are indexed to urinary creatinine due to variations in concentration, caution should be exercised when comparing groups with differing serum creatinine.

Oxidative stress response in pulmonary cells exposed to different fractions of PM2.5-0.3 from urban, traffic and industrial sites.

The aim of this work was to study the relationship between oxidative stress damages and particulate matter (PM) chemical composition, sources, and PM fractions. PM2.5-0.3 (PM with equivalent aerodynamic diameter between 2.5 and 0.3 µm) were collected at urban, road traffic and industrial sites in the North of France, and were characterized for major and minor chemical species. Four different fractions (whole PM2.5-0.3, organic, water-soluble and non-extractable matter) were considered for each of the PM2.5-0.3 samples from the three sites. After exposure of BEAS-2B cells to the four different fractions, oxidative stress was studied in cells by quantifying reactive oxygen species (ROS) accumulation, oxidative damage to proteins (carbonylated proteins), membrane alteration (8-isoprostane) and DNA damages (8-OHdG). Whole PM2.5-0.3 was capable of inducing ROS overproduction and caused damage to proteins at higher levels than other fractions. Stronger cell membrane and DNA damages were found associated with PM and organic fractions from the urban site. ROS overproduction was correlated with level of expression of carbonylated proteins, DNA damages and membrane alteration markers. The PM2.5-0.3 collected under industrial influence appears to be the less linked to cell damages and ROS production in comparison with the other influences.

Maternal Diet Quality and the Health Status of Newborns.

The maternal diet during pregnancy affects neonatal health status. The objective of this study was to assess the nutritional quality of the maternal diet, and its contamination by persistent organic pollutants (POPs), in pregnant women living in two areas of the Czech Republic with different levels of air pollution, and subsequently to assess the relationship of these two factors with birth weight and neonatal oxidative stress. To determine the level of oxidative stress, 8-isoprostane concentrations in umbilical cord plasma were measured. The overall nutritional quality of the maternal diet was not optimal. Of the nutritional factors, protein intake proved to be the most significant showing a positive relationship with birth weight, and a negative relationship with the oxidative stress of newborns. Dietary contamination by persistent organic pollutants was low and showed no statistically significant relationship with birth weight. Only one of the 67 analyzed POPs, namely the insecticide dichlorodiphenyltrichloroethane (DDT), showed a statistically significant positive relationship with the level of neonatal oxidative stress.

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).

Challenges in Quantifying 8-OHdG and 8-Isoprostane in Exhaled Breath Condensate.

Exhaled breath condensate (EBC) has attracted substantial interest in the last few years, enabling the assessment of airway inflammation with a non-invasive method. Concentrations of 8-Hydroxydesoxyguanosine (8-OHdG) and 8-isoprostane in EBC have been suggested as candidate biomarkers for lung diseases associated with inflammation and oxidative stress. EBC is a diluted biological matrix and consequently, requires highly sensitive chemical analytic methods (picomolar range) for biomarker quantification. We developed a new liquid chromatography coupled to tandem mass spectrometry method to quantify 8-OHdG and 8-isoprostane in EBC simultaneously. We applied this novel biomarker method in EBC obtained from 10 healthy subjects, 7 asthmatic subjects, and 9 subjects with chronic obstructive pulmonary disease. Both biomarkers were below the limit of detection (LOD) despite the good sensitivity of the chemical analytical method (LOD = 0.5 pg/mL for 8-OHdG; 1 pg/mL for 8-isoprostane). This lack of detection might result from factors affecting EBC collections. These findings are in line with methodological concerns already raised regarding the reliability of EBC collection for quantification of 8-OHdG and 8-isoprostane. Precaution is therefore needed when comparing literature results without considering methodological issues relative to EBC collection and analysis. Loss of analyte during EBC collection procedures still needs to be resolved before using these oxidative stress biomarkers in EBC.

Oxidative Stress in Chronic Obstructive Pulmonary Disease.

There is a marked increase in oxidative stress in the lungs of patients with COPD, as measured by increased exhaled 8-isoprostane, ethane, and hydrogen peroxide in the breath. The lung may be exposed to exogenous oxidative stress from cigarette smoking and indoor or outdoor air pollution and to endogenous oxidative stress from reactive oxygen species released from activated inflammatory cells, particularly neutrophils and macrophages, in the lungs. Oxidative stress in COPD may be amplified by a reduction in endogenous antioxidants and poor intake of dietary antioxidants. Oxidative stress is a major driving mechanism of COPD through the induction of chronic inflammation, induction of cellular senescence and impaired autophagy, reduced DNA repair, increased autoimmunity, increased mucus secretion, and impaired anti-inflammatory response to corticosteroids. Oxidative stress, therefore, drives the pathology of COPD and may increase disease progression, amplify exacerbations, and increase comorbidities through systemic oxidative stress. This suggests that antioxidants may be effective as disease-modifying treatments. Unfortunately, thiol-based antioxidants, such as N-acetylcysteine, have been poorly effective, as they are inactivated by oxidative stress in the lungs, so there is a search for more effective and safer antioxidants. New antioxidants in development include mitochondria-targeted antioxidants, NOX inhibitors, and activators of the transcription factor Nrf2, which regulates several antioxidant genes.

Unmasking the Confounder: The Inherent Physiologic Variability of Swine During an Automated Experimental Model of Ischemia-Reperfusion Injury.

BACKGROUND: We sought to determine the magnitude of the inherent inter-animal physiologic variability by automating a porcine Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) protocol to minimize external influences that might alter physiology and confound experimental results. METHODS: Swine (n = 42) underwent a controlled 30% blood volume hemorrhage followed by 30 minutes of REBOA (ie, ischemic phase). The animals were weaned from REBOA autonomously over 15 minutes, beginning the reperfusion phase, while continuing to provide partial flow balloon support to maintain a target proximal mean arterial pressure (pMAP) of 65 mmHg. Simultaneously, shed blood was re-transfused as part of the resuscitation efforts. Physiologic data were continuously recorded, and serum samples were serially collected. Baseline characteristics, variance in vital signs, and 8-isoprostane levels were quantified during hemorrhage, REBOA, and reperfusion phases. RESULTS: There was no significant difference in baseline physiology across animals (P > .05). Hemodynamic variability was highest for pMAP during the ischemic phase (P = .001) and for distal mean arterial pressure (dMAP) during the weaning/reperfusion phase (P = .001). The latter finding indicated the variable physiologic response to ischemia-reperfusion injury, as the automated balloon support required by each animal to maintain pMAP was highly variable. Circulating 8-isoprostane variance was significantly higher following the start of reperfusion compared to baseline levels (P = .001). DISCUSSION: Despite subjecting animals to a highly consistent ischemia-reperfusion injury through automation, we noted significant variability in the hemodynamic and biochemical response. These findings illustrate the inherent physiologic variability and potential limitations of porcine large animal models for the study of shock.

Effect of metformin on reducing platelet dysfunction in gestational diabetes mellitus: a randomized controlled trial.

Objectives: To evaluate the effect of metformin in improving platelet dysfunction in women with gestational diabetes mellitus (GDM). Patients and methods: A randomized controlled trial was conducted on pregnant women diagnosed with GDM. Singleton low-risk pregnancies meeting the inclusion criteria were randomly allocated at 27-31 weeks to receive metformin and placebo through the rest of pregnancy. Thirty-seven and 39 cases were recruited into the metformin group and the placebo group, respectively. MPVs, P-selectin, and 8-isoprostane levels were determined at the time of allocation and 6 weeks after treatment. Obstetric and neonatal outcomes were also assessed. Results: Most baseline characteristics of the two groups were comparable. The levels of P-selectin after 6 weeks of treatment were significantly higher in the metformin group (68.9 ± 14.4 vs 60.6 ± 11.3; P-value = 0.006), indicating more platelet activation. All of the obstetric and neonatal outcomes were comparable except that birth weight was significantly lower in the metformin group (3018 ± 364 g vs 3204 ± 393 g; P-value = 0.037). Conclusion: Metformin, in addition to diet and lifestyle modifications, does not improve or worsen oxidative stress and platelet dysfunction in women with GDM. Nevertheless, metformin significantly reduces fetal weight in women with GDM, theoretically preventing macrosomia.

Effects of Oxidative Damage during Ruesi Dadton Exercise in Mild Cognitive Impairment: Randomized Controlled Trial.

This study aimed to investigate the effect of biomarkers of oxidative stress (OS) in 8-isoprostane (8-iso) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) on mild cognitive impairment (MCI) during a 12-week Ruesi Dadton (RD) exercise. A total of 274 enrolled participants were classified into blocks based on age and formal educational years, and randomly assigned into two groups: RD and control (CON). The participants' cognitive functions were tested using Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores to screen for MCI. Urine samples of approximately 30 mL were collected from both groups pre- and post-intervention. All participants signed consent forms before participating in the program. Participants in the RD group were instructed to perform 15 postures of RD exercise in 60 min, three times a week for 12 weeks. A 2 × 2 (group × time) repeated multivariate analysis, with MoCA score, 8-iso, and 8-OH-dG as covariates, was performed to analyze the between-subject differences across group [V = 0.143, F(2,60) = 5.020, p = 0.010, d = 0.209] and within-subject differences across interaction between group [V = 0.143, F(2,60) = 5.020, p = 0.010, d = 0.408]. There were significant differences from univariate data regarding both 8-iso (F1,61 = 10.081, P = 0.002, d = 0.406) and 8-OH-dG (F(1,61) = 5.965, P = 0.018, d = 0.312) levels. Moreover, results from both biomarkers in the RD group revealed significant improvements in 8-iso (p < 0.001) and 8-OH-dG (p = 0.003), whereas there were no improvements in the CON group. In conclusion, RD decreased biomarkers of OS during 12 weeks of RD exercise in MCI. These results indicate that in MCI, RD could improve lipid peroxidation and DNA oxidation by 8-iso and 8-OH-dG, respectively.

Quantile-specific heritability of 8-isoprostane and the modulating effects of smoking, alcohol, cardiovascular disease and diabetes on 8-isoprostane-gene interactions.

BACKGROUND: Urinary 8-isoprostane provides a significantly heritable measure of oxidative stress. Prior reports suggest that genetic variants may modulate oxidative stress due to smoking, other environmental factors, and disease. Alternatively, these apparent modulations may reflect a dependence of genetic effects on 8-isoprostane concentrations. METHOD: To test whether genetic effects on 8-isoprostane concentrations are quantile-dependent, quantile-specific offspring-parent (ßOP) and full-sib regression slopes (ßFS) were estimated by applying quantile regression to the age- and sex-adjusted creatinine-standardized urinary 8-isoprostane concentrations of Framingham Heart Study families. Quantile-specific heritabilities were calculated as h2 = 2ßOP/(1+rspouse) and h2 = {(1+8rspouseßFS)0.5-1}/(2rspouse)). RESULTS: Spouse 8-isoprostane concentrations were weakly concordant (rspouse = 0.06). 8-isoprostane heritability (h2±SE) increased significantly with increasing percentiles of its distribution (Plinear trend = 0.0009, Pquadratic trend = 0.0007, Pcubic trend = 0.003) when estimated from ßOP, and when estimated from ßFS (Plinear trend = 0.005, Pquadratic trend = 0.09, Pcubic trend = 0.06). Compared to the 10th percentile, ßOP-estimated h2 was over 22-fold greater at the 90th percentile (Pdifference = 9.2 × 10-5), and 5.3-fold greater when estimated from ßFS (Pdifference = 0.004). Significantly higher 8-isoprostane heritability in smokers than nonsmokers (0.352 ± 0.147 vs. 0.061 ± 0.036, Pdifference = 0.01), and heavier than lighter drinkers (0.449 ± 0.216 vs. 0.078 ± 0.037, Pdifference = 0.01) were eliminated when corrected for the higher 8-isoprostane concentrations of the smokers and heavier drinkers. CONCLUSION: Heritability of oxidative stress as measured by 8-isoprostane is quantile-dependent, which may contribute to the larger reported effects on oxidative stress by UCP2 -866G > A, IL6 -572C > G and LTA 252A > G polymorphisms in smokers than nonsmokers, by the UCP2 -866G > A polymorphism in coronary heart disease patients, by the ESRRG rs1890552 A > G polymorphism in type 2 diabetics, by the CYBA 242C > T polymorphism after exercise training, by the PLIN 11482G > A/14995A > T haplotype before weight loss, and by the CYBA -930A > G and GSTP1 I105V haplotypes in patients with pulmonary edema.

Inhaled corticosteroids' effects on biomarkers in exhaled breath condensate and blood in patients newly diagnosed with asthma who smoke.

OBJECTIVE: Exposure to cigarette smoke complicates the treatment and management of asthma through a variety of inflammatory effects. This study aimed to investigate the differences between newly diagnosed cases of asthma in smokers and nonsmokers in terms of localized and systemic biomarkers following treatment with inhaled corticosteroids (ICS) or ICS in combination with a long-acting ß2 agonist (LABA). METHODS: Specimens of exhaled breath condensate (EBC) from newly diagnosed patients with asthma were used to quantify inflammation in the airways, while blood samples were used to assess systemic inflammation. In both samples, the levels of IL-6, LTB4, LTD4, and 8-isoprostane were measured and these were repeated after 3 months of treatment with ICS or ICS + LABA. RESULTS: Of the 20 patients, 10 (50%) were nonsmokers with asthma (NSA) and 10 (50%) smokers with asthma (SA). There was no statistically significant difference in the blood or EBC levels of IL-6, LTB4, LTD4, or 8-isoprostane between the groups prior to treatment. Only the decrease in 8-isoprostane level in the EBC samples was found to be significantly greater in the NSA group after treatment (for smokers, the change was 2.91 ± 23.22, while for nonsmokers it was -22.72 ± 33.12, p = 0.022). Post-treatment asthma control was significantly better in the NSA group (p = 0.033). CONCLUSION: Monitoring the alterations in 8-isoprostane levels in EBC in patients with asthma who smoke may be helpful in deciding on therapeutic management and switching treatments. Asthma control was better in nonsmokers than in smokers.

Isoprostane-8 and GDF-15 as novel markers of post-PE syndrome: Relation with prothrombotic factors.

BACKGROUND: Post-pulmonary embolism (PE) syndrome occurs in up to 50% of PE patients. The pathophysiology of this syndrome is obscure. OBJECTIVE: We investigated whether enhanced oxidative stress and prothrombotic state may be involved in post-PE syndrome. METHODS: We studied 101 normotensive noncancer PE patients (aged 56.5 ± 13.9 years) on admission, after 5-7 days and after a 3-month anticoagulation, mostly with rivaroxaban. A marker of oxidative stress, 8-isoprostane, endogenous thrombin potential, fibrinolysis proteins, clot lysis time (CLT) and fibrin clot permeability (Ks ), along with PE biomarkers, were determined. RESULTS: Patients who developed the post-PE syndrome (n = 31, 30.7%) had at baseline 77.6% higher N-terminal brain natriuretic propeptide and 46.8% higher growth differentiation factor 15, along with 14.1% longer CLT associated with 34.4% higher plasminogen activator inhibitor-1 as compared to subjects without post-PE syndrome (all P < .05). After 5-7 days, only hypofibrinolysis was noted in post-PE syndrome patients. When measured at 3 months, prolonged CLT and reduced Ks were observed in post-PE syndrome patients, accompanied by 23.8% higher growth differentiation factor 15 and 35.8% higher plasminogen activator inhibitor-1 (all P < .05). 8-isoprostane levels ≥108 pg/ml (odds ratio=4.36; 95% confidence interval 1.63-12.27) and growth differentiation factor 15 ≥ 1529 pg/ml (odds ratio=3.89; 95% confidence interval 1.29-12.16) measured at 3 months were associated with higher risk of developing post-PE syndrome. CONCLUSIONS: Enhanced oxidative stress and prothrombotic fibrin clot properties could be involved in the pathogenesis of the post-PE syndrome. Elevated growth differentiation factor 15 assessed at 3 months might be a new biomarker of this syndrome.