Urinary Oxidative Stress Biomarkers Research Articles

Blood plasma and urinary biomarkers of oxidative stress in cats with urethral obstruction

BackgroundThis study aimed to investigate variations of the oxidative status in cats affected by urethral obstruction (UO) under Feline Idiopathic Cystitis (FIC) and Bacterial Cystitis (BC), in comparison with a group of healthy subjects. In both groups, the levels of several markers (either direct or indirect) indicative of the oxidative attack and of the antioxidant response were analyzed on plasma and urine samples. In particular, the plasma samples were evaluated for nitric oxide (NO), hydroperoxides derived by reactive oxygen activity (d-ROMs test), superoxide anion (O2−), glutathione peroxidase activity (GPx), superoxide dismutase activity (SOD), and ferric reducing antioxidant power (FRAP test); while on urine the levels of NO, d-ROMs, FRAP, SOD, malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured. Urine of UO patients was also subjected to urine-culture test.ResultsThe analytical data on plasma showed that UO, independently of the FIC or BC etiology, induced the insurgence of oxidative stress conditions at the systemic level. In the urine of the UO patients, except for SOD that increased, the markers of redox status were markedly decreased due probably their compromised filtration, thus suggesting involvement of renal function (assessed also by the high levels of plasma creatinine and proteinuria) with no oxidative damage of the lower urinary tract. Moreover, the adoption of a novel oxidative stress index’ (OSI) allowed to establish, by means of a numerical value, the different degrees of oxidative stress conditions for single UO patients, both in terms of oxidative attack and antioxidant response.ConclusionsFeline urethral obstruction, induced by Idiopathic Cystitis and Bacterial Cystitis, causes oxidative stress conditions at the systemic level that do not interest the lower urinary tract. Despite to the high variability of the profiles of oxidative stress indexes both in healthy and UO patients, the determination of OSI made possible the evaluation of their single degrees of oxidative stress. Possibly the results of this investigation can be compared with those of correspondent pathologies both in humans and in other animal species.

Effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers in healthy 5-6-year-old children: a randomized controlled trial.

As children spend up to 9h a day in kindergarten, the main purpose of our study was to evaluate the effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers (OSBs) in healthy children. In the randomized control trial with a follow-up, healthy 5-6-year-old children from six kindergartens were randomly divided into a prototype group (PG, n = 40) and a control group (CG, n = 17). PG followed a 2-week antioxidant-rich kindergarten meal plan (breakfast, lunch, and two snacks), and CG followed their standard kindergarten meal plans. Outside the kindergartens, participants ate as usual. We used a consecutive 7-day dietary record inside and outside the kindergarten and the national dietary assessment tool OPEN to assess the total dietary antioxidant capacity (dTAC) of the consumed foods. Malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and four F2-isoprostane were measured in fasting urine on days 1 and 15. We also measured total antioxidant power (PAT) and hydroperoxides (d-ROMs) in fasting serum on day 15 and obtained the value of the oxidative stress index (OSI). We used a Welch two-sample t-test and multiple regression analysis to compare the prototype and control groups and a nonparametric Wilcoxon signed rank exact test to compare pre- and post-intervention results in urine. Antioxidant-rich kindergarten meals contributed to a significantly (p < 0.05) higher intake of dTAC in PG participants compared to standard meals in CG participants (8.6 vs. 2.8mmol/day). We detected a negative correlation between dTAC intake and d-ROMs and between dTAC intake and OSI (r = - 0.29, p = 0.043 and r = - 0.31, p = 0.032, respectively). A significant decrease in urinary 8-iso-15-prostaglandin-F-2 alpha was detected in PG participants between days 1 and 15; however, no other intra-individual significant differences in urinary OSBs were found. Conclusion: Antioxidant-rich food in kindergarten is warranted due to its potential health-protective effect. Additionally, we present original data on the average levels of urinary and serum OSBs in healthy 5-6-year-old children. Trial registration: The study was registered at ClinicalTrials.gov, on February 5, 2020 ( https://clinicaltrials.gov/ct2/show/NCT04252105 ). What is Known: • Kindergartens are recognized as promising environments for public health measures. • A diet rich in antioxidants can reduce OSBs and, consequently, the risk of developing NCDs. What is New: • Antioxidant-rich kindergarten diet can ensure a protective intake of dTAC in children. • Original data on serum oxidative stress biomarkers (d-ROMs, PAT, and OSI) and urinary oxidative stress biomarkers (MDA, 8-OHdG, and F2 isoprostanes) in healthy 5-6-year-old children.

Association of co-exposure to polycyclic aromatic hydrocarbons and phthalates with oxidative stress and inflammation

Exposure to multiple environmental pollutants is ubiquitous and inevitable, but studies investigating their exposure effects on oxidative stress or inflammation have mainly been restricted to single-pollutant models. This study investigated the association of co-exposure to polycyclic aromatic hydrocarbons and phthalates with oxidative stress and inflammation. Using a cross-sectional study in adults, we measured urinary concentrations of metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) and phthalates (mPAEs), urinary oxidative stress biomarker 8-hydroxy-2′-deoxyguanosine, and 9 inflammatory biomarkers in paired blood samples. The associations of urinary OH-PAHs and mPAEs with oxidative stress and inflammation biomarkers were evaluated by different statistical models. The Bayesian kernel machine regression and quantile g-computation was used to examine the joint effects, and increased levels of urinary concentrations of OH-PAHs and mPAEs were associated with elevated 8-hydroxy-2′-deoxyguanosine level and white blood cell counts. Exposure to polycyclic aromatic hydrocarbons contributed more significantly to inflammation, while exposure to phthalates contributed more to oxidative stress. Monoisobutyl phthalate was identified as the most significant metabolite contributing to elevated oxidative stress levels. 1-Hydroxypyrene was negatively associated with platelet, and monomethyl phthalate was significantly positively associated with interleukin 6 in multivariate linear regression. The restricted cubic spline analysis revealed non-linear patterns of 3-hydroxyfluorene with white blood cell, lymphocyte, neutrophil, and C-reactive protein. The results indicated significant associations between increased co-exposure to polycyclic aromatic hydrocarbons and phthalates with elevated oxidative stress and inflammation. Further investigation is needed to elucidate the underlying biological mechanisms and to determine the potential public health implications.

Pulmonary, inflammatory, and oxidative effects of indoor nitrogen dioxide in patients with COPD.

Indoor nitrogen dioxide (NO2) sources include gas heating, cooking, and infiltration from outdoors. Associations with pulmonary function, systemic inflammation, and oxidative stress in patients with chronic obstructive pulmonary disease (COPD) are uncertain. We recruited 144 COPD patients at the VA Boston Healthcare System between 2012 and 2017. In-home NO2 was measured using an Ogawa passive sampling badge for a week seasonally followed by measuring plasma biomarkers of systemic inflammation (C-reactive protein [CRP] and interleukin-6 [IL-6]), urinary oxidative stress biomarkers (8-hydroxy-2'deoxyguanosine [8-OHdG] and malondialdehyde [MDA]), and pre- and postbronchodilator spirometry. Linear mixed effects regression with a random intercept for each subject was used to assess associations with weekly NO2. Effect modification by COPD severity and by body mass index (BMI) was examined using multiplicative interaction terms and stratum-specific effect estimates. Median (25%ile, 75%ile) concentration of indoor NO2 was 6.8 (4.4, 11.2) ppb. There were no associations observed between NO2 with CRP, 8-OHdG, or MDA. Although the confidence intervals were wide, there was a reduction in prebronchodilator FEV1 and FVC among participants with more severe COPD (FEV1: -17.36 mL; -58.35, 23.60 and FVC: -28.22 mL; -91.49, 35.07) that was greater than in patients with less severe COPD (FEV1: -1.64 mL; -24.80, 21.57 and FVC: -6.22 mL; -42.16, 29.71). In participants with a BMI <30, there was a reduction in FEV1 and FVC. Low-level indoor NO2 was not associated with systemic inflammation or oxidative stress. There was a suggestive association with reduced lung function among patients with more severe COPD and among patients with a lower BMI.

Organophosphate Flame Retardants Mixture associated with Increased Urinary Oxidative Stress Biomarkers among School Children: The Hokkaido Study

Organophosphate Flame Retardants Mixture associated with Increased Urinary Oxidative Stress Biomarkers among School Children: The Hokkaido Study

Exploring the relationship between urinary phthalate metabolites and Crohn's disease via oxidative stress, and the potential moderating role of gut microbiota: A conditional mediation model

ObjectiveInteractions between phthalic acid esters (PAEs) exposure and Crohn's disease (CD) were unknown. This study aims to examine the association between exposure to PAEs and CD activity and to explore the roles of oxidative stress and microbiota. MethodsA cross-sectional study with 127 CD patients was conducted. The disease activity was evaluated based on symptoms (Harvey-Bradshaw index, HBI), endoscopy findings (Simple Endoscopic Score for CD, SES-CD), and computed tomography enterography (CTE-scores). Ten urinary PAEs metabolites (mPAEs), two urinary oxidative stress biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α), as well as 16S rRNA sequencing of stool samples were determined. Multiple linear regression models and Hayes's PROCESS macro for SPSS were used to evaluate the interplays between urinary PAEs metabolites, CD activities, oxidative stress, and microbiota diversity. ResultsThere were positive associations between most mPAEs and HBI. Oxidative stress mediated 20.69–89.29% of the indirect associations between low molecular weight (LMW) mPAEs and HBI, while the majority of the high molecular weight (HMW) mPAEs were directly associated with HBI. In addition, microbiota diversity moderated the indirect associations of LMW mPAEs on HBI. ConclusionsPAEs exposure was related to CD activity, and the association could be mediated by oxidative stress and reversed or alleviated by rich gut microbiota.

Exposure to multiple neonicotinoid insecticides, oxidative stress, and gestational diabetes mellitus: Association and potential mediation analyses

As the most extensively used insecticides worldwide, neonicotinoid insecticides (NNIs) have received a growing global concern over their adverse health effects. This study aimed to assess the associations of urinary concentrations of NNIs in early pregnancy with gestational diabetes mellitus (GDM) and the mediation roles of oxidative DNA damage, RNA damage, and lipid peroxidation in the associations. With a prospective nested case-control study, 519 GDM cases and 519 controls were matched on the infant’s sex and maternal age. Urinary biomarkers of NNIs exposure and oxidative stress were measured in early pregnancy. We estimated the associations of single and the mixture of NNIs and their metabolites with GDM by conditional logistic regression and quantile g-computation models, respectively. The mediating roles of oxidative stress were evaluated by the structural equation model. The odds of GDM significantly increased by 15 %, 18 %, 26 %, 42 %, 49 %, and 13 % in each unit increment of ln-transformed concentrations of urinary imidacloprid (IMI), imidacloprid-olefin (IMI-olefin), desnitro-imidacloprid (DN-IMI), thiamethoxam (THM), clothianidin, and desmethyl-clothianidin, respectively. Exposure to the mixture of NNIs was associated with increased odds of GDM (adjusted OR: 1.76; 95 %CI: 1.45, 2.13). Advanced maternal age enhanced the associations of 5-hydroxy-IMI, DN-IMI, and IMI-olefin with GDM (P < 0.05), and being overweight/obese before pregnancy strengthened the effects of IMI, IMI-olefin, and THM on GDM (P < 0.05). In the association of NNIs exposure and GDM, the proportions mediated by oxidative DNA damage, RNA damage, and overall oxidative stress were 9.8 %, 11.8 %, and 14.5 %, respectively (P < 0.05). Exposure to individual NNIs and a mixture of NNIs were associated with GDM, and maternal age and pre-pregnancy BMI may modify the association. The possible mechanism underlying the association between NNIs and GDM may involve oxidative damage to nucleic acids.

Indoor (residential) and ambient particulate matter associations with urinary oxidative stress biomarkers in a COPD cohort

ObjectivesOxidative stress contributes to chronic obstructive pulmonary disease (COPD) pathophysiology. Associations between indoor (residential) exposure to particulate matter ≤2.5 μm in diameter (PM2.5) and one of its components, black carbon (BC), and oxidative stress are ill-defined. MethodsBetween 2012 and 2017, 140 patients with COPD completed in-home air sampling over one week intervals, followed by collection of urine samples to measure oxidative stress biomarkers, malondialdehyde (MDA), a marker of lipid peroxidation, and 8-hydroxy-2′ -deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Ambient (central site) BC and PM2.5 were measured, and the ratio of indoor/ambient sulfur in PM2.5, a surrogate for residential ventilation and particle infiltration, was used to estimate indoor BC and PM2.5 of outdoor origin. Mixed effects linear regression models with a participant-specific random intercept were used to assess associations with oxidative biomarkers, adjusting for personal characteristics. ResultsThere were positive associations (% increase per IQR; 95 % CI) of directly measured indoor BC with total MDA (6.96; 1.54, 12.69) and 8-OHdG (4.18; −0.67, 9.27), and similar associations with both indoor BC of outdoor origin and ambient BC. There were no associations with directly measured indoor PM2.5, but there were positive associations between indoor PM2.5 of outdoor origin and total MDA (5.40; −0.91, 12.11) and 8-OHdG (8.02; 2.14, 14.25). ConclusionsIn homes with few indoor combustion sources, directly measured indoor BC, estimates of indoor BC and PM2.5 of outdoor origin, and ambient BC, were positively associated with urinary biomarkers of oxidative stress. This suggests that the infiltration of particulate matter from outdoor sources, attributable to traffic and other sources of combustion, promotes oxidative stress in COPD patients.

Prenatal oxidative stress and rapid infant weight gain.

Infant weight patterns predict subsequent weight outcomes. Rapid infant weight gain, defined as a >0.67 increase in weight-for-age z-score (WAZ) between two time points in infancy, increases obesity risk. Higher oxidative stress, an imbalance between antioxidants and reactive oxygen species, has been associated with low birthweight and paradoxically also with later obesity. We hypothesized that prenatal oxidative stress may also be associated with rapid infant weight gain, an early weight pattern associated with future obesity. Within the NYU Children's Health and Environment Study prospective pregnancy cohort, we analyzed associations between prenatal lipid, protein, and DNA urinary oxidative stress biomarkers and infant weight data. Primary outcome was rapid infant weight gain (>0.67 increase in WAZ) between birth and later infancy at the 8 or 12 month visit. Secondary outcomes included: very rapid weight gain (>1.34 increase in WAZ), low (<2500 g) or high (≥4000 g) birthweight, and low (< -1 WAZ) or high (>1 WAZ) 12 month weight. Pregnant participants consented to the postnatal study (n = 541); 425 participants had weight data both at birth and in later infancy. In an adjusted binary model, prenatal 8-iso-PGF2α, a lipid oxidative stress biomarker, was associated with rapid infant weight gain (aOR 1.44; 95% CI: 1.16, 1.78, p = 0.001). In a multinomial model using ≤0.67 change in WAZ as a reference group, 8-iso-PGF2α was associated with rapid infant weight gain (defined as >0.67 but ≤1.34 WAZ; aOR 1.57, 95% CI: 1.19, 2.05, p = 0.001) and very rapid infant weight gain (defined as >1.34 WAZ; aOR 1.33; 95% CI: 1.02, 1.72, p < 0.05) Secondary analyses detected associations between 8-iso-PGF2α and low birthweight outcomes. We found an association between 8-iso-PGF2α, a lipid prenatal oxidative stress biomarker, and rapid infant weight gain, expanding our understanding of the developmental origins of obesity and cardiometabolic disease.

PD23-04 URINARY PROTEINS IN THE DIAGNOSIS OF MIXED INTRINSIC SPHINCTER DEFICIENCY AND DETRUSOR OVERACTIVITY IN FEMALE PATIENTS WITH STRESS URINARY INCONTINENCE?

You have accessJournal of UrologyCME1 Apr 2023PD23-04 URINARY PROTEINS IN THE DIAGNOSIS OF MIXED INTRINSIC SPHINCTER DEFICIENCY AND DETRUSOR OVERACTIVITY IN FEMALE PATIENTS WITH STRESS URINARY INCONTINENCE? Wei-Hsin Chen, Yuan-Hong Jiang, and Hann-Chorng Kuo Wei-Hsin ChenWei-Hsin Chen More articles by this author , Yuan-Hong JiangYuan-Hong Jiang More articles by this author , and Hann-Chorng KuoHann-Chorng Kuo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003296.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To investigate urinary biomarkers in women with stress urinary incontinence (SUI). METHODS: We retrospectively enrolled 93 female patients with SUI. The patients were categorized into the following three groups based on video-urodynamic findings: intrinsic sphincter deficiency (ISD) and detrusor overactivity (DO), ISD and hypersensitive bladder (HSB), and ISD and stable bladder (controls) groups. RESULTS: The mean age of the cohort was 60.8±10.7 (36–83) years (Table 1). Thirty-one (33.3%), 28 (30.1%), and 34 (36.6%) patients were included in the ISD and DO, ISD and HSB, and control groups, respectively. The ISD and DO group had significantly increased 8-isoprostane (mean, 33.285 vs. 10.795 pg/mL) and 8-hydroxy-2-deoxyguanosine (8-OHdG; mean, 28.912 vs. 17.416 ng/mL) and decreased interleukin (IL)-2 (mean, 0.433 vs. 0.638 pg/mL), vascular endothelial growth factor (mean, 5.506 vs. 8.989 pg/mL), and neural growth factor (mean, 0.175 vs. 0.235 pg/mL) levels than the controls (Figure 1). The analytes from controls were moderately diagnostic of DO, except for 8-isoprostane [area under the curve (AUC) >0.7]. Voided volume was highly diagnostic of DO from either controls or non-DO patients (AUC 0.750 and 0.915 respectively). The proposed prediction model with voided volume, 8-OHdG, and 8-isoprostane (cutoff values of 384 ml, 35 ng/mL, and 37 pg/mL, respectively) had an accuracy of 81.72% (sensitivity, 67.74%; specificity, 88.71%; positive predictive value, 75.00%; and negative predictive value, 84.62%). CONCLUSIONS: Combined with voided volume, urinary oxidative stress biomarkers have the potential to be used to identify urodynamic DO in patients with SUI. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e671 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wei-Hsin Chen More articles by this author Yuan-Hong Jiang More articles by this author Hann-Chorng Kuo More articles by this author Expand All Advertisement PDF downloadLoading ...

Urinary Oxidative Stress Biomarker Levels Might Be Useful in Identifying Functional Bladder Disorders in Women with Frequency and Urgency Syndrome.

lower urinary tract dysfunctions (LUTDs) are difficult to diagnose based on symptoms. This study used a cluster of urinary biomarkers, including inflammatory cytokines, neurogenic proteins, and oxidative stress biomarkers, to identify LUTDs in women with frequency and urgency symptoms. in total, 253 women with video urodynamics (VUDS)- and cystoscopy-confirmed detrusor overactivity (DO), interstitial cystitis/bladder pain syndrome (IC/BPS), dysfunctional voiding (DV), and hypersensitive bladder (HSB), and normal controls were included. Before diagnosis and treatment, urine samples were collected for analysis of biomarkers. The urine levels of biomarkers were compared between groups with bladder dysfunctions and controls and were combined to test the sensitivity in identifying total pathological bladder diseases and specific bladder diseases. After video urodynamic study, VUDS, and urological examinations, bladder dysfunctions were classified into DO (n = 31), IC/BPS (n = 114), DV (n = 45), HSB (n = 29), and control (n = 34) groups. By using a cystomeric bladder capacity of ≤350 mL, 186/219 (84.9%) of the patients with DO, IC/BPS, DV, and HSB can be discriminated from the controls. Among these urine biomarkers, oxidative stress biomarkers 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), or total antioxidant capacity (TAC) are useful for identifying pathological bladder dysfunction (DO, IC/BPS, and DV) and HSB. With elevated IL-1β and lower IL-2, and elevated TNF-α levels, most patients with DV can be identified. Between DO and IC/BPS, a higher NGF level can identify 58.3% of IC/BPS cases, whereas a lower NGF level can identify 75.0% of DO cases. by using a cluster of urine biomarkers, DO, IC/BPS, and DV cases can be identified based on elevated levels of urine oxidative stress biomarkers 8-isoprostane, TAC, or 8-OHdG, and HSB cases with a low TAC. These urine biomarkers are useful for identifying specific LUTDs in women with frequency and urgency symptoms.

Urinary Oxidative Stress Biomarkers in the Diagnosis of Detrusor Overactivity in Female Patients with Stress Urinary Incontinence.

Ninety-three women with urodynamic stress incontinence (USI) and a mean age of 60.8 ± 10.7 (36-83) years were retrospectively enrolled. According to their VUDS, 31 (33%) were grouped into USI and detrusor overactivity (DO), 28 (30.1%) were grouped into USI and hypersensitive bladder (HSB), and 34 (36.6%) were controls (USI and stable bladder). The USI and DO group had significantly increased 8-isoprostane (mean, 33.3 vs. 10.8 pg/mL) and 8-hydroxy-2-deoxyguanosine (8-OHdG; mean, 28.9 vs. 17.4 ng/mL) and decreased interleukin (IL)-2 (mean, 0.433 vs. 0.638 pg/mL), vascular endothelial growth factor (mean, 5.51 vs. 8.99 pg/mL), and nerve growth factor (mean, 0.175 vs. 0.235 pg/mL) levels compared to controls. Oxidative stress biomarkers were moderately diagnostic of DO from controls, especially 8-isoprostane (area under the curve (AUC) > 0.7). Voided volume was highly diagnostic of DO from either controls or non-DO patients (AUC 0.750 and 0.915, respectively). The proposed prediction model with voided volume, 8-OHdG, and 8-isoprostane (cutoff values 384 mL, 35 ng/mL, and 37 pg/mL, respectively) had an accuracy of 81.7% (sensitivity, 67.7%; specificity, 88.7%; positive predictive value, 75.0%; negative predictive value, 84.6%). Combined with voided volume, urinary oxidative stress biomarkers have the potential to be used to identify urodynamic DO in patients with USI.

Glyphosate exposure and urinary oxidative stress biomarkers in the Agricultural Health Study.

Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study. This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male nonfarmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α, and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable linear regression to evaluate associations of urinary glyphosate and self-reported glyphosate use with each oxidative stress biomarker. Urinary glyphosate concentrations were positively associated with levels of 8-OHdG (highest vs lowest glyphosate quartile; geometric mean ratio = 1.15, 95% confidence interval = 1.03 to 1.28; Ptrend = .02) and MDA (geometric mean ratio = 1.20, 95% confidence interval = 1.03 to 1.40; Ptrend = .06) overall. Among farmers reporting recent glyphosate use (last 7 days), use in the previous day was also associated with statistically significantly increased 8-OHdG and MDA levels. Compared with nonfarmers, we observed elevated 8-iso-prostaglandin-F2α levels among farmers with recent, high past 12-month, or high lifetime glyphosate use. Our findings contribute to the weight of evidence supporting an association between glyphosate exposure and oxidative stress in humans and may inform evaluations of the carcinogenic potential of this herbicide.

Urinary oxidative stress biomarkers are associated with preterm birth: an Environmental Influences on Child Health Outcomes program study

Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States. We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin. This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F2α, 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F2α (F2-IsoP-M; the major 8-iso-prostaglandin-F2α metabolite), and prostaglandin-F2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models. Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F2-IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis. Here, oxidative stress, as measured by 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation.

Associations between urinary biomarkers of oxidative stress and biomarkers of tobacco smoke exposure in smokers

Oxidative stress can contribute to the development of diseases, and may originate from exposures to toxicants commonly found in air pollution and cigarette smoke such as polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs). Yet, associations between these exposures and oxidative stress biomarkers are poorly characterized. We report here novel associations between 14 exposure biomarkers of PAHs and VOCs, and two oxidative stress biomarkers; 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-isoprostaglandin F2α (8-isoprostane) in urine obtained from smokers participating in an ongoing clinical study (ESTxENDS, NCT03589989). We also assessed associations between six biomarkers of tobacco smoke exposure (metabolites of nicotine and tobacco-specific nitrosamines (TSNAs)) and both oxidative stress biomarkers. We then quantified the relative importance of each family of the 20 exposure biomarkers on oxidative stress. Participating smokers (153 men and 117 women, median age 44 years) had on average smoked 25 [2–62] years and smoked about 17 [5–40] cigarettes per day at the time of the study. Multiple linear regression results showed an association between 8-oxodG concentrations and the following metabolites in decreasing relative importance: PAHs (beta coefficient β = 0.105, p-value <0.001, partial R2 = 0.15) > VOCs (β = 0.028, p < 0.001, partial R2 = 0.09) > nicotine (β = 0.226, p < 0.001, partial R2 = 0.08); and between 8-isoprostane concentrations and metabolites of PAHs (β = 0.117, p < 0.001, partial R2 = 0.14) > VOCs (β = 0.040, p < 0.001, partial R2 = 0.14) > TSNAs (β = 0.202, p = 0.003, partial R2 = 0.09) > nicotine (β = 0.266, p < 0.001, partial R2 = 0.08). Behavioral factors known to contribute to oxidative stress, including sleep quality, physical activity, and alcohol consumption, did not play a significant role. Exposures to PAHs and VOCs among smokers were significantly associated with oxidative stress.

Associations between repeated measures of urinary phthalate metabolites and biomarkers of oxidative stress in a rural agricultural cohort of children with asthma

Phthalate exposure is widespread, and studies suggest an adverse relationship with asthma morbidity, including some support for oxidative stress as an underlying pathophysiological mechanism. Urinary phthalate metabolites have been associated with biomarkers of oxidative stress, but data are few in children diagnosed with asthma. We used participant data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine longitudinal relationships between phthalates and oxidative stress in a cohort of Latino children with asthma residing in an agricultural community. We used linear mixed-effects models to estimate associations between 11 urinary phthalate metabolites (and one summed measure of di-2-ethylhexyl phthalate (DEHP) metabolites, ∑DEHP) and two urinary biomarkers of oxidative stress: a biomarker of lipid peroxidation via measure of 8-isoprostane and a biomarker of DNA/RNA oxidative damage via combined measure of 8-hydroxydeoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 8-hydroxyguanine. Seventy-nine participants provided 281 observations. In covariate-adjusted models, we observed significant positive relationships between all phthalate metabolites and 8-isoprostane, effect sizes ranging from a 9.3 % (95 % CI: 4.2 %–14.7 %) increase in 8-isoprostane for each 100 % increase (i.e., doubling) of mono-(carboxy-isooctyl) phthalate (MCIOP), to a 21.0 % (95 % CI: 14.3 %–28.2 %) increase in 8-isoprostane for each doubling of mono-n-butyl phthalate (MNBP). For each doubling of mono-(carboxy-isononyl) phthalate (MCINP) and mono-ethyl phthalate (MEP), the DNA/RNA oxidative damage biomarker increased by 6.0 % (95 % CI: 0.2 %–12.2 %) and 6.5 % (95 % CI: 1.4 %–11.9 %), respectively. In conclusion, we provide unique data suggesting phthalate exposure is positively associated with oxidative stress in children with asthma. Our repeat measures provide novel identification of a consistent effect of phthalates on oxidative stress in children with asthma via lipid peroxidation. Confirmation in future studies of children with asthma is needed to enhance understanding of the role of phthalates in childhood asthma morbidity.

Exposure to lead-free frangible firing emissions containing copper and ultrafine particulates leads to increased oxidative stress in firing range instructors

BackgroundSince the introduction of copper based, lead-free frangible (LFF) ammunition to Air Force small arms firing ranges, instructors have reported symptoms including chest tightness, respiratory irritation, and metallic taste. These symptoms have been reported despite measurements determining that instructor exposure does not exceed established occupational exposure limits (OELs). The disconnect between reported symptoms and exposure limits may be due to a limited understanding of LFF firing byproducts and subsequent health effects. A comprehensive characterization of exposure to instructors was completed, including ventilation system evaluation, personal monitoring, symptom tracking, and biomarker analysis, at both a partially enclosed and fully enclosed range.ResultsInstructors reported symptoms more frequently after M4 rifle classes compared to classes firing only the M9 pistol. Ventilation measurements demonstrated that airflow velocities at the firing line were highly variable and often outside established standards at both ranges. Personal breathing zone air monitoring showed exposure to carbon monoxide, ultrafine particulate, and metals. In general, exposure to instructors was higher at the partially enclosed range compared to the fully enclosed range. Copper measured in the breathing zone of instructors, on rare occasions, approached OELs for copper fume (0.1 mg/m3). Peak carbon monoxide concentrations were 4–5 times higher at the partially enclosed range compared to the enclosed range and occasionally exceeded the ceiling limit (125 ppm). Biological monitoring showed that lung function was maintained in instructors despite respiratory symptoms. However, urinary oxidative stress biomarkers and urinary copper measurements were increased in instructors compared to control groups.ConclusionsConsistent with prior work, this study demonstrates that symptoms still occurred despite exposures below OELs. Routine monitoring of symptoms, urinary metals, and oxidative stress biomarkers can help identify instructors who are particularly affected by exposures. These results can assist in guiding protective measures to reduce exposure and protect instructor health. Further, a longitudinal study is needed to determine the long-term health consequences of LFF firing emissions exposure.

Urinary Biomarkers of Oxidative Stress in Aging: Implications for Prediction of Accelerated Biological Age in Prospective Cohort Studies.

Background Aging is a major risk factor for a range of chronic diseases. Oxidative stress theory of aging has been previously proposed as one of the mechanisms responsible for the age-related decline in organ/tissue function and the development of age-related diseases. Urine contains rich biological information on the health status of every major organ system and can be an important noninvasive source for biomarkers of systemic oxidative stress in aging. Aims The objective of this cross-sectional study was to validate a novel panel of urinary oxidative stress biomarkers. Methods Nucleic acid oxidation adducts and oxidative damage markers of lipids and proteins were assessed in urine samples from nondiabetic and currently nonsmoking subjects (n = 198) across different ages (20 to 89 years old). Urinary parameters and chronological age were correlated then the biological age of enrolled individuals was determined from the urinary oxidative stress markers using the algorithm of Klemera and Doubal. Results Our findings showed that 8-oxo-7,8-deoxyguanosine (8-oxoG), 8-oxo-7,8-dihydroguanosine (8-OHdG), and dityrosine (DTyr) positively correlated with chronological age, while the level of an F2-isoprostane (iPF2α-VI) correlated negatively with age. We found that 8-oxoG, DTyr, and iPF2α-VI were significantly higher among accelerated agers compared to nonaccelerated agers and that a decision tree model could successfully identify accelerated agers with an accuracy of >92%. Discussion. Our results indicate that 8-oxoG and iPF2α-VI levels in the urine reveal biological aging. Conclusion Assessing urinary biomarkers of oxidative stress may be an important approach for the evaluation of biological age by identifying individuals at accelerated risk for the development of age-related diseases.

Elevated Urinary Biomarkers of Oxidative Damage in Photocopier Operators following Acute and Chronic Exposures.

Inhalation exposures to nanoparticles (NPs) from printers and photocopiers have been associated with upper airway and systemic inflammation, increased blood pressure, and cases of autoimmune and respiratory disorders. In this study we investigate oxidative stress induced by exposures to copier-emitted nanoparticles using a panel of urinary oxidative stress (OS) biomarkers representing DNA damage (8-hydroxydeoxyguanosine, 8-OHdG; 8-hydroxyguanosine, 8-OHG; 5-hydroxymethyl uracil 5-OHMeU), lipid peroxidation (8-isoprostane; 4-hydroxynonenal, HNE), and protein oxidation biomarkers (o-tyrosine, 3-chlorotyrosine, and 3-nitrotyrosine) under conditions of acute (single 6 h exposure, 9 volunteers, 110 urine samples) and chronic exposures (6 workers, 11 controls, 81 urine samples). Urinary biomarkers were quantified with liquid chromatography–tandem mass spectrometry after solid phase extraction sample cleanup. 8-OHdG, 8-OHG, 8-isoprostane, and HNE were significantly elevated in both the acute and chronic exposure study participants relative to the controls. In the acute exposure study, the geometric mean ratios post-/pre-exposure were 1.42, 1.10, 2.0, and 2.25, respectively. Urinary 8-OHG and HNE increased with time to at least 36 h post-exposure (post-/pre-exposure GM ratios increased to 3.94 and 2.33, respectively), suggesting slower generation and/or urinary excretion kinetics for these biomarkers. In chronically exposed operators, the GM ratios of urinary biomarkers relative to controls ranged from 1.52 to 2.94, depending on the biomarker. O-Tyrosine and 5-OHMeU biomarkers were not significantly different from the controls. 3-chlorotyrosine and 3-nitrotyrosine were not detected in the urine samples. We conclude that NPs from photocopiers induce systemic oxidative stress by damaging DNA, RNA, and lipids. Urinary levels of 8-OHdG, 8-OHG, HNE, and 8-isoprostane were orders of magnitude higher than in nanocomposite processing workers, comparable to nano titanium dioxide and fiberglass manufacturing workers, but much lower than in shipyard welding and carbon nanotube synthesis workers. Biomarkers 8-OHdG, 8-OHG, 8-isoprostane, and HNE appear to be more sensitive and robust urinary biomarkers for monitoring oxidative stress to NPs from photocopiers.

The association between urinary glyphosate and aminomethyl phosphonic acid with biomarkers of oxidative stress among pregnant women in the PROTECT birth cohort study

BackgroundGlyphosate is a widely used herbicide in global agriculture. Glyphosate and its primary environmental degradate, aminomethyl phosphonic acid (AMPA), have been shown to disrupt endocrine function and induce oxidative stress in in vitro and animal studies. To our knowledge, these relationships have not been previously characterized in epidemiological settings. Elevated urinary levels of glyphosate and AMPA may be indicative of health effects caused by previous exposure via multiple mechanisms including oxidative stress. MethodsGlyphosate and AMPA were measured in 347 urine samples collected between 16 and 20 weeks gestation and 24–28 weeks gestation from pregnant women in the PROTECT birth cohort. Urinary biomarkers of oxidative stress, comprising 8-isoprostane-prostaglandin-F2α (8-iso-PGF2α), its metabolite 2,3-dinor-5,6-dihydro-15-F2 t-isoprostane (8-isoprostane metabolite) and prostaglandin-F2α (PGF2α), were also measured. Linear mixed effect models assessed the association between exposures and oxidative stress adjusting for maternal age, smoking status, alcohol consumption, household income and specific gravity. Potential nonlinear trends were also assessed using tertiles of glyphosate and AMPA exposure levels. ResultsNo significant differences in exposure or oxidative stress biomarker concentrations were observed between study visits. An interquartile range (IQR) increase in AMPA was associated with 9.5% (95% CI: 0.5–19.3%) higher 8-iso-PGF2α metabolite concentrations. Significant linear trends were also identified when examining tertiles of exposure variables. Compared to the lowest exposure group, the second and third tertiles of AMPA were significantly associated with 12.8% (0.6–26.5%) and 15.2% (1.8–30.3%) higher 8-isoprostane metabolite, respectively. An IQR increase in glyphosate was suggestively associated with 4.7% (−0.9 to 10.7%) higher 8-iso-PGF2α. ConclusionsUrinary concentrations of the main environmental degradate of glyphosate, AMPA, were associated with higher levels of certain oxidative stress biomarkers. Associations with glyphosate reflected similar trends, although findings were not as strong. Additional research is required to better characterize the association between glyphosate exposure and biomarkers of oxidative stress, as well as potential downstream health consequences.