Impact of heat-not-burn cigarette passive smoking on children's oxidative stress, endothelial and platelet function.

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2-18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient ß: 0.284; SE: 0.040; p = 0.01) and H2O2 (standardized coefficient ß: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient ß:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient ß:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.

Preconception Phthalate Exposure and Women's Reproductive Health: Pregnancy, Pregnancy Loss, and Underlying Mechanisms.

BACKGROUND: Phthalates are endocrine-disrupting chemicals linked to adverse pregnancy outcomes. Despite the sensitivity of female reproductive processes to oxidation-reduction reaction stress and endocrine disruption, evidence for the impact of women's phthalate exposure on the ability to establish and maintain pregnancy has been inconclusive. OBJECTIVES: We aimed to determine the relationship of preconception phthalate metabolite exposure with a) fecundability and pregnancy loss and b) markers of potential biological mechanisms, including reproductive hormones, inflammation, and oxidative stress. METHODS: Data were collected from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a preconception study following 1,228 women who were attempting pregnancy, for up to six menstrual cycles and throughout pregnancy if they became pregnant. Twenty phthalate metabolites were measured in a consecutive 3-d pooled urine sample at enrollment. Pregnancy was determined through urinary human chorionic gonadotropin (hCG) at the expected date of menses during each cycle and pregnancy loss as an observed loss following positive hCG. Highly sensitive C-reactive protein (hsCRP) and isoprostanes were measured at enrollment, and reproductive hormones were measured during the follicular phase, ovulation, and luteal phase. Discrete-time Cox proportional hazards models evaluated the relationship of phthalate metabolites with fecundability and weighted Poisson models with robust variance evaluated the risk of pregnancy loss. RESULTS: An interquartile range (IQR) higher mono-(2-ethylhexyl) phthalate [fecundability odds ratio (FOR)=0.88; 95% confidence interval (CI): 0.78, 1.00], mono-butyl phthalate (FOR=0.82; 95% CI: 0.70, 0.96), and mono-benzyl phthalate (FOR=0.85; 95% CI: 0.74, 0.98) was associated with lower fecundability. No consistent associations were observed with pregnancy loss. Preconception phthalates were consistently associated with higher hsCRP and isoprostanes, as well as lower estradiol and higher follicle-stimulating hormone across the menstrual cycle. DISCUSSION: Women's preconception exposure to phthalates was associated with lower fecundability, changes in reproductive hormones, and increased inflammation and oxidative stress. The pre- and periconception periods may represent sensitive windows for intervening to limit the reproductive toxicity of phthalate exposure. https://doi.org/10.1289/EHP12287.

Inter-individual variability in redox and performance responses after antioxidant supplementation: A randomized double blind crossover study.

AIM: We aimed to investigate the inter-individual variability in redox and physiological responses of antioxidant-deficient subjects after antioxidant supplementation. METHODS: Two hundred individuals were sorted by plasma vitamin C levels. A low vitamin C group (n = 22) and a control group (n = 22) were compared in terms of oxidative stress and performance. Subsequently, the low vitamin C group received for 30 days vitamin C (1 g) or placebo, in randomized, double-blind, crossover fashion, and the effects were examined through a mixed-effects model, while individual responses were calculated. RESULTS: The low vitamin C group exhibited lower vitamin C (-25 µmol/L; 95%CI[-31.7, -18.3]; p < 0.001), higher F2 -isoprostanes (+17.1 pg/mL; 95%CI[6.5, 27.7]; p = 0.002), impaired VO2max (-8.2 mL/kg/min; 95%CI[-12.8, -3.6]; p < 0.001) and lower isometric peak torque (-41.5 Nm; 95%CI[-61.8, -21.2]; p < 0.001) compared to the control group. Regarding antioxidant supplementation, a significant treatment effect was found in vitamin C (+11.6 µmol/L; 95%CI[6.8, 17.1], p < 0.001), F2 -isoprostanes (-13.7 pg/mL; 95%CI[-18.9, -8.4], p < 0.001), VO2max (+5.4 mL/kg/min; 95%CI[2.7, 8.2], p = 0.001) and isometric peak torque (+18.7; 95%CI[11.8, 25.7 Nm], p < 0.001). The standard deviation for individual responses (SDir) was greater than the smallest worthwhile change (SWC) for all variables indicating meaningful inter-individual variability. When a minimal clinically important difference (MCID) was set, inter-individual variability remained for VO2max , but not for isometric peak torque. CONCLUSION: The proportion of response was generally high after supplementation (82.9%-95.3%); however, a few participants did not benefit from the treatment. This underlines the potential need for personalized nutritional interventions in an exercise physiology context.

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.

A method for improved detection of 8-isoprostaglandin F2α/ß and benzodiazepines in wastewater.

Wastewater-based epidemiology is a tool incorporating biomarker analysis that can be used to monitor the health status of a population. Indicators of health include endogenous oxidative stress biomarkers and hormones, or exogenous such as alcohol and nicotine. 8-Iso-prostaglandin F2α/ß is a biomarker of endogenous metabolism that can be used to measure oxidative stress in a community. Benzodiazepines are a harmful subclass of anxiolytics either prescribed or sourced illegally. The analysis of oxidative stress markers and uptake of benzodiazepines in wastewater may provide information about distress in the community. A method has been applied to detect 8-isoPGF2α/ß and the illicit benzodiazepines clonazolam, flubromazolam and flualprazolam in addition to other prescribed benzodiazepines in wastewater. These substances have been sold as counterfeit pharmaceutical products, such as Xanax, which was formulated to include alprazolam. Deconjugation was initially performed on wastewater samples, followed by liquid-liquid extraction for isoprostanes and solid phase extraction for benzodiazepines to determine the total levels of these analytes. Limits of quantification were in the range of 0.5-2 ng/L for all the analytes except 8-isoPGF2α/ß which was 50 ng/L. Stability, recovery and matrix effect studies were also conducted. Finally, this method was applied to influent wastewater from South Australia which showed the prevalence of 8-isoPGF2α/ß and benzodiazepines.

Assessment of the association of exposure to polycyclic aromatic hydrocarbons, oxidative stress, and inflammation: A cross-sectional study in Augsburg, Germany.

BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to acute and chronic health effects through the suggested pathways of oxidative stress and inflammation. However, evidence is still limited. We aimed to investigate jointly the relationship of PAHs, oxidative stress, and inflammation. METHODS: We measured 13 biomarkers of PAH exposure (n = 6: hydroxylated polycyclic aromatic hydrocarbons, [OH-PAHs]), oxidative stress (n = 6: malondialdehyde (MDA); 8-hydroxy-2'-deoxyguanosine (8-OHdG); and 4 representatives of the compound class of F2α-isoprostanes) in urine, and inflammation (n = 1: high-sensitivity C-reactive protein, [hs-CRP]) in serum from 400 participants at the second follow-up (2013/2014) of the German KORA survey S4. Multiple linear regression models were applied to investigate the interplay between biomarkers. RESULTS: Concentrations of biomarkers varied according to sex, age, smoking status, season, and a history of obesity, diabetes, or chronic kidney disease. All OH-PAHs were significantly and positively associated with oxidative stress biomarkers. An interquartile range (IQR) increase in sum OH-PAHs was associated with a 13.3% (95% CI: 9.9%, 16.9%) increase in MDA, a 6.5% (95% CI: 3.5%, 9.6%) increase in 8-OHdG, and an 8.4% (95% CI: 6.6%, 11.3%) increase in sum F2α-isoprostanes. Associations were more pronounced between OH-PAHs and F2α-isoprostanes but also between OH-PAHs and 8-OHdG for participants with potential underlying systemic inflammation (hs-CRP ≥ 3 mg/L). We observed no association between OH-PAHs and hs-CRP levels. While 8-OHdG was significantly positively associated with hs-CRP (13.7% [95% CI: 2.2%, 26.5%] per IQR increase in 8-OHdG), F2α-isoprostanes and MDA indicated only a positive or null association, respectively. CONCLUSION: The results of this cross-sectional study suggest, at a population level, that exposure to PAHs is associated with oxidative stress even in a low exposure setting. Oxidative stress markers, but not PAHs, were associated with inflammation. Individual risk factors were important contributors to these processes and should be considered in future studies. Further longitudinal studies are necessary to investigate the causal chain of the associations.

Evidence for Indoxyl Sulfate as an Inducer of Oxidative Stress in Patients With Diabetes.

BACKGROUND/AIM: Indoxyl sulfate is a metabolite of tryptophan and its urinary level reflects the status of bacterial flora in the intestine. Indoxyl sulfate possesses prooxidant properties and is implicated in various diseases including chronic kidney disease and cardiovascular diseases. However, the relation of urinary indoxyl sulfate to oxidative stress is not known. PATIENTS AND METHODS: The association of urinary indoxyl sulfate levels with urinary levels of oxidative stress markers, 15-isoprostane F2t and pteridine derivatives, was investigated in 255 patients with type 2 diabetes. Indoxyl sulfate and pteridine derivatives were measured by using spectrofluorometry. RESULTS: Urinary levels of indoxyl sulfate, pteridines, and 15-isoprostane F2t showed a normal distribution after logarithmic transformation but not before it, and they were thus used for parametric analysis after logarithmic transformation. Urinary indoxyl sulfate levels were significantly correlated (p<0.01) with urinary 15-isoprostane F2t and pteridine levels [Pearson's correlation coefficients: 0.503 (15-isoprostane F2t) and 0.562 (pteridines)]. These associations were also found in multivariable analysis after adjusting for age, sex, insulin therapy for diabetes, body mass index, mean arterial pressure, hemoglobin A1c, estimated glomerular filtration rate, urinary albumin, and histories of smoking and alcohol drinking. CONCLUSION: Urinary indoxyl sulfate levels showed associations with urinary levels of oxidative stress markers, and the associations were independent of age, sex, insulin therapy for diabetes, body mass index, blood pressure, glycemic status, renal function, smoking, and alcohol drinking. Indoxyl sulfate appears to be an important determinant of redox balance in patients with diabetes.

Associations between social, biologic, and behavioral factors and biomarkers of oxidative stress during pregnancy: Findings from four ECHO cohorts.

BACKGROUND: Lower socioeconomic status (SES) and elevated psychosocial stress are known contributors to adverse pregnancy outcomes; however, biological mechanisms linking these factors to adverse pregnancy outcomes are not well-characterized. Oxidative stress may be an important, yet understudied mechanistic pathway. We used a pooled study design to examine biological, behavioral, and social factors as predictors of prenatal oxidative stress biomarkers. METHODS: Leveraging four pregnancy cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program spanning multiple geographic regions across the United States (U.S.) (N = 2082), we measured biomarkers of oxidative stress in urine samples at up to three time points during pregnancy, including 8-isoprostane-prostaglandin F2α (8-isoPGF2α), its major metabolite, 2,3-dinor-5,6-dihydro-15-F2t-isoprostane, and prostaglandin F2α (PGF2α). Maternal age, pre-pregnancy body mass index, marital/partnered status, parity, and smoking status were included as biological and behavioral factors while race/ethnicity, maternal education, and stressful life events were considered social factors. We examined associations between each individual biological, behavioral, and social factor with oxidative stress biomarkers using multivariable-adjusted linear mixed models. RESULTS: Numerous biological, behavioral, and social factors were associated with elevated levels of 8-isoPGF2α, its major metabolite, and PGF2α. Pregnant people who were current smokers relative to non-smokers or had less than a high school education relative to a college degree had 11.04% (95% confidence interval [CI] = -1.97%, 25.77%) and 9.13% (95% CI = -1.02%, 20.32%) higher levels of 8-isoPGF2α, respectively. CONCLUSIONS: Oxidative stress biomarkers are elevated among pregnant people with higher socioeconomic disadvantage and may represent one pathway linking biological, behavioral, and social factors to adverse pregnancy and child health outcomes, which should be explored in future work.

Association of dietary and plasma carotenoids with urinary F2-isoprostanes.

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

Evidence for Systemic Reactive Oxygen Species in UVB-mediated Microvesicle Formation.

Recent studies have implicated subcellular microvesicle particles (MVP) in the ability of ultraviolet B radiation to exert both local and systemic effects. Indeed, UVB generates MVP (UVB-MVP) in human skin and systemically following phototherapy. The current studies were designed to test the hypothesis that the ability of UVB to generate MVP was dependent upon reactive oxygen species (ROS). To that end, we tested urine samples from subjects undergoing UVB phototherapy for the presence of isoprostanes as well as the oxidized guanosine derivative 8OHdG. We also conducted a clinical study in which volar forearms of subjects were treated with localized UVB and erythema/MVP measured. The same cohort was then treated with 7 days of vitamin C (2 g day-1 ) and vitamin E (1000 IU day-1 ), and UVB-induced MVPs tested on the contralateral forearm. Urine specimens from subjects undergoing phototherapy were found to have increased levels of isoprostanes and 8OHdG, with maximal levels noted 8-16 h post-treatment. Treatment with antioxidant vitamins resulted in diminished UVB-generated skin MVP to baseline levels. These studies suggest that whole-body UVB generates a systemic pro-oxidative response, and that antioxidants can attenuate localized skin UVB-MVPs.

Impact of heat stress on embryonic development during first 16 days of gestation in dairy cows.

Objective was to elucidate the effects of heat stress (HS) on embryo development during first 16 gestational days (GD) and circulating hormone concentrations on GD-16 in lactating Holstein cows. Cows in HS and control (CON) groups were exposed to temperature humidity index (THI) of ≥ 73 and < 73, respectively, for 3 weeks before the experiment. GD-7 (67 vs 49%) and GD-16 (52 vs. 31%) conception rates following single insemination were greater (P < 0.01) for CON compared with HS cows. Control cows produced more GD-7 transferrable embryos following superovulation compared with HS cows (84.8 vs 53.1%; P < 0.001). Mean (± SEM) length (45.2 ± 10.6 vs. 59.2 ± 9.1 mm) and weight (31.4 ± 4.3 vs. 42.4 ± 6.2 mg) of GD-16 conceptus were greater for CON compared with HS cows (P < 0.05). Control cows yielded more filamentous conceptus (≥ 25 mm) compared with HS cows (71 vs 45%; P < 0.05). Progesterone (2.09-fold) was higher, and cortisol (1.86-fold), prolactin (1.60-fold), substance-P (1.55-fold), Isoprostane-8 (1.34-fold) and prostaglandin F metabolites (1.97-fold) were lower in CON compared with HS cows (P < 0.05). Progesterone positively, and substance-P, isoprostane-8 and the THI negatively were associated with GD-16 conceptus length (P < 0.05). In conclusion, altered hormones concentrations in heat-stressed cows plausibly resulted in lower GD-7 and GD-16 conception rates, fewer GD-7 transferable embryos, and stunted GD-16 conceptus elongation.

Plasma and urinary F2-isoprostane markers of oxidative stress are increased in cats with early (stage 1) chronic kidney disease.

OBJECTIVES: Oxidative stress contributes to chronic kidney disease (CKD) progression in humans and rodent models; F2-isoprostanes (F2-IsoPs) are established biomarkers of oxidative stress. Our primary aim was to evaluate plasma F2-IsoPs in cats with International Renal Interest Society stage 1 and 2 CKD, compared with healthy cats, and to determine whether plasma and urinary F2-IsoPs are equivalent biomarkers. The secondary aim was to assess whether consumption of a renal diet enriched in omega-3 fatty acids led to improvements in plasma and urinary F2-IsoPs. METHODS: Plasma and urinary F2-IsoPs were measured in 24 cats with stage 1 or 2 CKD, and 12 unaffected controls aged ⩾6 years. Twelve CKD cats were re-evaluated after feeding a commercial renal diet for at least 4 weeks. RESULTS: Median plasma F2-IsoPs were significantly higher in stage 1 CKD (96.2 pg/ml), early stage 2 CKD (83.2 pg/ml) and late stage 2 CKD (80.8 pg/ml) compared with healthy cats (22.8 pg/ml; P = 0.03-0.002). Median urinary F2-IsoPs were significantly higher in cats with stage 1 CKD (231.2 pg/mg) compared with healthy cats (152.5 pg/mg) or cats with late stage 2 CKD (124.8 pg/mg; P = 0.01). Plasma F2-IsoPs remained increased, while urinary F2-IsoPs fell with transition from stage 1 to stage 2 CKD. Feeding a commercial renal diet led to significant decreases in plasma F2-IsoPs in the small group of cats with stage 1 CKD (25-75% decrease) compared with cats with stage 2 CKD (20% decrease to 53% increase; P = 0.01). CONCLUSIONS AND RELEVANCE: Oxidative stress is prominent in cats with stage 1 CKD. Plasma and urinary F2-IsoPs are not interchangeable biomarkers in cats with stage 2 CKD. Placebo-controlled studies are indicated to evaluate dietary or pharmacologic doses of omega-3 fatty acids on redox stress and progression of renal dysfunction in cats with stage 1 CKD.

Assessment of urinary 15-F2 -isoprostanes in dogs with urothelial carcinoma of the urinary bladder and other lower urinary tract diseases.

BACKGROUND: The 15-F2 -isoprostanes are by-products of oxidative stress and are increased in the urine of people with lower urinary tract diseases (LUTD), especially urinary neoplasia. Urothelial carcinoma (UC) is the most common urinary neoplasm in dogs. Earlier detection of UC by noninvasive means could lead to improved outcomes. Urinary 15-F2 -isoprostanes potentially could provide this means, but have not been evaluated in dogs with UC. OBJECTIVE: The objective of this study was to measure urinary 15-F2 -isoprostanes in dogs with UC and dogs with other LUTD. ANIMALS: One hundred seventeen dogs: 46 dogs with UC, 30 dogs with LUTD, and 25 control dogs. METHODS: Any dog that was presented with dysuria was eligible for inclusion. Diagnosis of UC was confirmed histologically. Urinalysis was performed in each case, and 15-F2 -isoprostanes quantified by gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NICI-MS) and normalized to urinary creatinine concentration. RESULTS: Dogs with urinary diseases (UC + LUTD) had higher median urinary 15-F2 -isoprostanes when compared to control dogs (5.92 ng/mg [range, 0.46-31.03] vs 3.73 [range, 1.8-7.98]; P = .02). Urinary 15-F2 -isoprostanes were similar in dogs with UC (5.33 ng/mg [range, 0.46-31.03]) compared to dogs with LUTD (6.29 ng/mg [range, 0.54-18.93]; P = .47) and control dogs (P = .06). Dogs with UC had higher qualitative measures of proteinuria (P = .004), hematuria (P = .01), and epithelial cells on urinalysis (P = .002) compared to the other groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary F2 -isoprostanes are not useful for the detection of UC in dogs. Future research could evaluate urinary 15-F2 -isoprostanes as a marker of inflammation in disease progression and prognosis.

Effects of diets high in corn oil or in extra virgin olive oil on oxidative stress in an experimental model of breast cancer.

Experimental evidence highlights the importance of dietetic factors on breast cancer. In this work we aimed to analyze the effects two oils, corn oil (rich in n-6 polyunsaturated fatty acids -PUFA-) and extra virgin olive oil (EVOO), on oxidative stress in an animal model of breast carcinogenesis. Female rats were fed a low-fat control, a high-corn oil, or a high-EVOO diet from weaning or after induction with 7,12-dimethylbenz[a]anthracene at 53 days. Animals were euthanized at 36, 51, 100 and 246 days of age. We analyzed antioxidant enzymes (mRNA and activity of superoxide dismutase, glutathione peroxidase and catalase), non-enzymatic capacity (oxidized and reduced glutathione) and DNA damage (8-oxo-dG) in tumors and mammary gland at different ages. We also analyzed lipid peroxidation (isoprostanes in serum and lipofuscin in liver). Results indicated a decrease in the enzymatic antioxidant capacity and increased oxidative stress in mammary gland of healthy young animals after a short period of high-fat diets intake, followed by an adaptation to chronic dietary intervention. After induction both diets, especially the one high in n-6 PUFA, increased the oxidized glutathione. In tumors no clear effects of the high-fat diets were observed, although in the long-term lipofuscin and 8-oxo-dG suggested greater oxidative damage by effect of the n-6 PUFA-rich diet. Considering the differential effects of these diets on mammary carcinogenesis that we have previously reported, this study suggests that these high-fat diets could have an effect on oxidative stress that would lead to different signaling pathways.

Influence of feeding thermally peroxidized soybean oil on growth performance, digestibility, gut integrity, and oxidative stress in nursery pigs.

The objectives of the current experiments were to evaluate the effect of feeding soybean oil (SO) with different levels of peroxidation on lipid, N, and GE digestibility, gut integrity, oxidative stress, and growth performance in nursery pigs. Treatments consisted diets containing 10% fresh SO (22.5 °C) or thermally processed SO (45 °C for 288 h, 90 °C for 72 h, or 180 °C for 6 h), each with an air infusion of 15 L/min, with postprocessing peroxide values of 7.6, 11.5, 19.1, and 13.4 mEq/kg and p-anisidine values of 1.92, 6.29, 149, and 159, for the 22.5 °C, 45 °C, 90 °C and 180 °C processed SO, respectively. In experiment 1, 64 barrows (7.1 ± 0.9 kg initial BW) were randomly allotted into 2 rooms of 32 pens and individually fed their experimental diets for 21 d, with a fresh fecal sample collected on day 20 for determination of GE and lipid digestibility. In experiment 2, 56 barrows (BW 9.16 ± 1.56 kg) were placed into individual metabolism crates for assessment of GE, lipid, and N digestibility and N retention. Urinary lactulose to mannitol ratio was assessed to evaluate in vivo small intestinal integrity, and urine and plasma were collected to analyze for markers of oxidative stress. Pigs were subsequently euthanized to obtain liver weights and analyze the liver for markers of oxidative stress. In experiment 1, pigs fed the SO thermally processed at 90 °C had reduced ADG (P = 0.01) and ADFI (P = 0.04) compared to pigs fed the other SO treatment groups, with no differences noted among pigs fed the 22.5 °C, 45 °C, and 180 °C SO treatments. No effects of feeding thermally processing SO on dietary GE or lipid digestibility (P > 0.10) were noted in either experiment. In experiment 2, there was no dietary effect of feeding peroxidized SO on the DE:ME ratio, N digestibility, or N retained as a percent of N digested, on the urinary ratio of lactulose to mannitol, on serum, urinary, or liver thiobarbituric acid reactive substances, on plasma protein carbonyls, or on urinary or liver 8-OH-2dG (P > 0.10). In experiment 2, pigs fed the SO thermally processed at 90 °C had the greatest isoprostane concentrations in the serum (P ≤ 0.01) and urine (P ≤ 0.05) compared to pigs fed the unprocessed SO. These results indicate that the change in fatty acid composition and/or the presence of lipid peroxidation products in peroxidized SO may reduce ADG and ADFI in nursery pigs, but appears to have no impact on GE, lipid, or N digestibility, or gut permeability. These data suggest that the presence of lipid peroxidation products may affect certain markers of oxidative stress.

Peripheral artery disease and oxidative stress in patients in a program for preventing complications of diabetes mellitus and dyslipidemia / Enfermedad arterial periférica y estrés oxidativo en pacientes del programa para la prevención de complicaciones de diabetes mellitus y dislipidemias

Abstract Introduction: Peripheral artery disease (PAD) is mainly caused by atherosclerosis but also involves hyperglycemia and dyslipidemia, which trigger oxidative stress and lead to vascular damage. Objectives: To determine the prevalence of PAD in patients with type 2 diabetes mellitus (DM2) and/or prediabetes and/or dyslipidemia, to identify some risk factors and to establish whether urinary levels of 8-isoprostane-f2α (an oxidative stress marker) are elevated in patients with PAD. Design: A cross-sectional, nonprobabilistic, convenience sampling study Materials and methods: The sample included 146 patients with DM2 and/or prediabetes and/ or dyslipidemias from the Universidad Nacional de Colombia. Risk factors, symptoms related to PAD, ankle-brachial index measurement and biochemical variables (HbA1c%, fasting blood glucose, lipid profile, creatinine and albuminuria) were recorded. Urine levels of 8-isoprostane-f2α were determined by ELISA. The 8-iso-PGF2α/creatine concentration were analyzed using the statistical package R. Risk factors were compared using ANOVA/ Kruskal-Wallis. ROC curves were generated to analyze the discriminant power of the biomarkers. The joint analysis of laboratory results and risk factors was performed using multivariate logistic regressions. Results: PAD was identified in 10 diabetic patients. Risk factors were smoking, dyslipidemia, poor metabolic control, overweight or obesity. There was no evidence of increased urinary 8-isoprostane-f2α in these subjects. Conclusions: A low prevalence of PAD was found in subjects with DM2. There was no evidence of increased 8-isoprostane-f2α measured by ELISA in patients with PAD. The extension of the study with different markers of oxidative stress and the use of other techniques is recommended (Acta Med Colomb 2019; 44. DOI: https://doi.org/10.36104/amc.2019.1257).

Resumen Introducción: la enfermedad arterial periférica (EAP) es causada principalmente por aterosclerosis e intervienen la hiperglucemia y dislipidemia que desencadenan estrés oxidativo y daño vascular. Objetivo: determinar la prevalencia de EAP en pacientes con diabetes mellitus tipo 2 (DM2) y/o prediabetes y/o dislipidemias, así como algunos factores de riesgo; también, establecer si los niveles urinarios de 8-isoprostano-f2α (marcador de estrés oxidativo) están elevados en pacientes con EAP. Diseño: estudio de tipo transversal, no probabilístico, de conveniencia. Material y métodos: la muestra comprendió 146 pacientes con DM2 y/o prediabetes y/o dislipidemias de la Universidad Nacional de Colombia. Se registraron factores de riesgo, síntomas relacionados con EAP, medida índice tobillo-brazo y variables bioquímicas (HbA1c%, glucemia basal, perfil lipídico, creatinina y albuminuria). Se determinaron niveles en orina de 8-isoprostano-f2α por ELISA. Los resultados de la concentración de 8-iso-PGF2α/creatinuria se analizaron mediante el paquete estadístico R. La comparación de factores de riesgo se analizó mediante ANOVA/Kruskal-Wallis. Se generaron curvas ROC para analizar el poder discriminante del biomarcador. El análisis conjunto de resultados de laboratorios y de factores de riesgo se realizó mediante regresiones logísticas multivariantes. Resultados: se evidenció prevalencia de EAP en 10 pacientes diabéticos. Como factores de riesgo se encontraron: fumar, dislipidemia, mal control metabólico, sobrepeso u obesidad. No se evidenció aumento del 8-isoprostano-f2α urinario en estos sujetos. Conclusiones: se encontró baja prevalencia de EAP en los sujetos con DM2. No se evidenció aumento del 8-isoprostano-f2α medido por ELISA en pacientes con EAP. Se recomienda ampliar el estudio con diferentes marcadores de estrés oxidativo y uso de otras técnicas. (Acta Med Colomb 2019; 44. DOI: https://doi.org/10.36104/amc.2019.1257).

Associations between socioeconomic status, psychosocial stress, and urinary levels of 8-iso-prostaglandin-F2α during pregnancy in Puerto Rico.

BACKGROUND: Lower socioeconomic status (SES) and psychosocial stress during pregnancy have been associated with adverse birth outcomes. While hypothalamic-pituitary-axis activation is thought to be the primary driver, oxidative stress may also be involved mechanistically. We used data from the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort (N=476) to examine associations between self-reported psychosocial stress measures, SES indicators, and urinary oxidative stress biomarker concentrations, hypothesizing that women with lower SES and increased psychosocial stress would have elevated oxidative stress biomarkers. METHODS: Maternal age, education, marital status, insurance status, alcohol use and smoking status were obtained via self-reported questionnaires and were used as indicators of SES. Perceived stress, depression, negative life experiences, neighborhood perceptions, and social support were self-reported in questionnaires administered during pregnancy. Responses were grouped into tertiles for analysis, where the highest tertile corresponded to highest level of psychosocial stress. Urinary concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α) and its primary metabolite were measured at three study visits (median 18, 24, 28 weeks gestation) and averaged to reflect oxidative stress across pregnancy. Linear models were used to examine associations between SES indicators, tertiles of psychosocial stress and oxidative stress biomarkers. RESULTS: Average levels of 8-iso-PGF2α and the 8-iso-PGF2α metabolite were higher among pregnant women who were younger, who had public compared to private insurance, and who were unemployed compared to employed. However, no associations were observed between psychosocial stress measures and biomarker concentrations in adjusted analyses. CONCLUSIONS: Psychosocial stress during pregnancy, as indicated by self-reported questionnaire measures, was not associated with biomarkers of oxidative stress in the PROTECT study. However, results suggest that these biomarkers are elevated among women of lower SES, which is typically associated with stress. Notably, compared to other populations, self-reported psychosocial stress measures were lower in PROTECT compared to other populations.

Improvement of asthma control after laser acupuncture and its impact on exhaled 8-isoprostane as an oxidative biomarker in chronic bronchial asthma.

Traditional medicine may not control bronchial asthma. Many patients have uncontrolled symptoms and the underlying ongoing inflammation is persistent. OBJECTIVE: to assess efficacy of laser acupuncture in improving asthma symptoms and underlying oxidative stress through monitoring exhaled 8-isoprostane. METHOD: 48 asthmatic (case group) received successive low level laser acupuncture sessions to stimulate acupoints for chronic asthma and 24 asthmatics received deactivated laser acupuncture sessions (control group). Asthma symptoms, asthma control questionnaire, concentration of 8-Isoprostane in exhaled breath condensate and airway resistance were assessed before and after laser acupuncture therapy. RESULTS: After the completion of the course of laser acupuncture therapy, we observed significant improvement of asthma symptoms. Asthma control questionnaire improved from 9.7 ±â€¯3.3 to 21.8 ±â€¯3.6 (p 0.001). EBC 8-Isoprostane dropped from 14.7 ±â€¯5.4 to 8.1 ±â€¯5.0 (p 0.001). The airway resistance at R5 and R20 significantly decreased from 116.6 ±â€¯25.8 & 124.5 ±â€¯31.2 to 101.5 ±â€¯25.6 &110.9 ±â€¯29.9 respectively (p 0.001). Control patients who received sham acupuncture therapy did not show such improvement. CONCLUSION: Laser acupuncture is an effective modality in treating bronchial asthma as evidenced by improved symptoms, airway resistance, and oxidative biomarkers.

Erythrocyte and plasma oxidative stress appears to be compensated in patients with sickle cell disease during a period of relative health, despite the presence of known oxidative agents.

Sickle cell disease (SCD) is a monogenetic disease that results in the formation of hemoglobin S. Due to more rapid oxidation of hemoglobin S due to intracellular heme and adventitious iron in SCD, it has been thought that an inherent property of SCD red cells would be an imbalance in antioxidant defenses and oxidant production. Less deformable and fragile RBC in SCD results in intravascular hemolysis and release of free hemoglobin (PFHb) in the plasma, which might be expected to produce oxidative stress in the plasma. Thus, we aimed to characterize intracellular and vascular oxidative stress in whole blood and plasma samples from adult SCD patients and controls recruited into a large study of SCD at Children's Hospital of Los Angeles. We evaluated the cellular content of metHb and several components of the antioxidant system in RBC as well as oxidation of GSH and Prx-2 oxidation in RBC after challenge with hydroperoxides. Plasma markers included PFHb, low molecular weight protein bound heme (freed heme), hemopexin, isoprostanes, and protein carbonyls. While GSH was slightly lower in SCD RBC, protein carbonyls, NADH, NAD+ and total NADP+ + NADPH were not different. Furthermore, GSH or Prx-2 oxidation was not different after oxidative challenge in SCD vs. Control. Elevated freed heme and PFHb had a significant negative, non-linear association with hemopexin. There appeared to be a threshold effect for hemopexin (200 µg/ml), under which the freed heme rose acutely. Plasma F2-isoprostanes were not significantly elevated in SCD. Despite significant release of Hb and elevation of freed heme in SCD when hemopexin was apparently saturated, there was no clear indication of uncompensated vascular oxidative stress. This somewhat surprising result, suggests that oxidative stress is well compensated in RBCs and plasma during a period of relative health.

Oxidative stress - Related spontaneous preterm delivery challenges in causality determination, prevention and novel strategies in reduction of the sequelae.

Spontaneous preterm birth (PTB) is one of the major complications of pregnancy and the main cause of neonatal mortality and morbidity. Despite the efforts devoted to the understanding of this obstetrical syndrome and improved medical care, there has been a tendency for the PTB rate to increase in the last decades globally. The costs of the screening for spontaneous PTB, its management, and treatment of the sequelae represent a major burden to the health service economy of high-income countries. In this scenario, it has been widely acknowledged that oxidative stress (OS) plays an important role in the pathogenicity of human disease in wide range of areas of medicine. There is an emerging evidence that an imbalance between pro-and-antioxidants may be associated with spontaneous PTB. However, there are still many controversies on the mechanisms by which OS are involved in the pathogenesis of prematurity. Moreover, the crucial question whether the OS is the cause or consequence of the disease is yet to be answered. The purpose of this article is to briefly summarize the current knowledge and controversies on oxidative stress-related spontaneous PTB and to give a critical approach on future perspectives on this topic as a classical example of translational medicine. Placenta-mediated pregnancy adverse outcome associated with OS leading to iatrogenic PTB (e.g. pre-eclampsia, intrauterine growth restriction, gestational diabetes) will not be discussed.