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American Journal of Obstetrics and... May 2017Preeclampsia is a prevalent and enigmatic disease, in part characterized by poor remodeling of the spiral arteries. However, preeclampsia does not always clinically... (Comparative Study)
Comparative Study
BACKGROUND
Preeclampsia is a prevalent and enigmatic disease, in part characterized by poor remodeling of the spiral arteries. However, preeclampsia does not always clinically present when remodeling has failed to occur. Hypotheses surrounding the "second hit" that is necessary for the clinical presentation of the disease focus on maternal inflammation and oxidative stress. Yet, the studies to date that have investigated these factors have used cross-sectional study designs or small study populations.
OBJECTIVE
In the present study, we sought to explore longitudinal trajectories, beginning early in gestation, of a panel of inflammation and oxidative stress markers in women who went on to have preeclamptic or normotensive pregnancies.
STUDY DESIGN
We examined 441 subjects from the ongoing LIFECODES prospective birth cohort, which included 50 mothers who experienced preeclampsia and 391 mothers with normotensive pregnancies. Participants provided urine and plasma samples at 4 time points during gestation (median, 10, 18, 26, and 35 weeks) that were analyzed for a panel of oxidative stress and inflammation markers. Oxidative stress biomarkers included 8-isoprostane and 8-hydroxydeoxyguanosine. Inflammation biomarkers included C-reactive protein, the cytokines interleukin-1β, -6, and -10, and tumor necrosis factor-α. We created Cox proportional hazard models to calculate hazard ratios based on time of preeclampsia diagnosis in association with biomarker concentrations at each of the 4 study visits.
RESULTS
In adjusted models, hazard ratios of preeclampsia were significantly (P<.01) elevated in association with all inflammation biomarkers that were measured at visit 2 (median, 18 weeks; hazard ratios, 1.31-1.83, in association with an interquartile range increase in biomarker). Hazard ratios at this time point were the most elevated for C-reactive protein, for interleukin-1β, -6, and -10, and for the oxidative stress biomarker 8-isoprostane (hazard ratio, 1.68; 95% confidence interval, 1.14-2.48) compared to other time points. Hazard ratios for tumor necrosis factor-α were consistently elevated at all 4 of the study visits (hazard ratios, 1.49-1.63; P<.01). In sensitivity analyses, we observed that these associations were attenuated within groups typically at higher risk of experiencing preeclampsia, which include African American mothers, mothers with higher body mass index at the beginning of gestation, and pregnancies that ended preterm.
CONCLUSIONS
This study provides the most robust data to date on repeated measures of inflammation and oxidative stress in preeclamptic compared with normotensive pregnancies. Within these groups, inflammation and oxidative stress biomarkers show different patterns across gestation, beginning as early as 10 weeks. The start of the second trimester appears to be a particularly important time point for the measurement of these biomarkers. Although biomarkers alone do not appear to be useful in the prediction of preeclampsia, these data are useful in understanding the maternal inflammatory profile in pregnancy before the development of the disease and may be used to further develop an understanding of potentially preventative measures.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; C-Reactive Protein; Cohort Studies; Cytokines; Deoxyguanosine; Dinoprost; Female; Humans; Inflammation; Oxidative Stress; Pre-Eclampsia; Pregnancy; Proportional Hazards Models
PubMed: 28043842
DOI: 10.1016/j.ajog.2016.12.174 -
Paediatric and Perinatal Epidemiology Jul 2018Prenatal psychological stress during pregnancy has been associated with adverse reproductive outcomes. A growing animal literature supports an association between...
BACKGROUND
Prenatal psychological stress during pregnancy has been associated with adverse reproductive outcomes. A growing animal literature supports an association between psychological stress and oxidative stress. We assessed this relationship in pregnant women, hypothesising that psychological stress is associated with higher concentrations of oxidative stress biomarkers during pregnancy.
METHODS
Psychosocial status and stressful life events (SLE) were self-reported. 8-iso-prostaglandin F (8-iso-PGF ) was measured as a biomarker of oxidative stress in urine samples at median 32 weeks' gestation. We examined SLEs individually (ever vs never) and in summary (any vs none) and psychosocial status as measured by individual subscales and in summary (poor vs good). Linear models estimated associations between these parameters and urinary 8-iso-PGF concentrations after adjusting for covariates.
RESULTS
The geometric mean of 8-iso-PGF was significantly higher among pregnant women who were non-White, smokers, had less than a college education, higher pre-pregnancy BMI and were unmarried. Having ever had a death in the family (n = 39) during pregnancy was associated with a 22.9% increase in 8-iso-PGF in unadjusted models (95% confidence interval [CI] 1.50, 48.8). Poor psychosocial status was associated with a 13.1% (95% CI 2.43, 25.0) greater mean 8-iso-PGF in unadjusted analyses. Associations were attenuated, but remained suggestive, after covariate adjustment.
CONCLUSIONS
These data suggest that 8-iso-PGF is elevated in pregnant women with who are at a sociodemographic disadvantage and who have higher psychological stress in pregnancy. Previous studies have observed that 8-iso-PGF levels are associated with adverse birth outcomes, oxidative stress could be a mediator in these relationships.
Topics: Adult; Biomarkers; Case-Control Studies; Dinoprost; Female; Humans; Lipid Peroxidation; Oxidative Stress; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Social Class; Stress, Psychological
PubMed: 29603338
DOI: 10.1111/ppe.12465 -
International Journal of Chronic... 2007
Topics: Biomarkers; Breath Tests; Dinoprost; Humans; Leukotriene B4; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results
PubMed: 18044058
DOI: 10.2147/copd.2007.2.1.2 -
American Journal of Physiology. Heart... Dec 2006To determine the mechanism(s) underlying enhanced oxidative stress in kidneys of salt-sensitive hypertension, neonatal Wistar rats were given vehicle or capsaicin (CAP,...
To determine the mechanism(s) underlying enhanced oxidative stress in kidneys of salt-sensitive hypertension, neonatal Wistar rats were given vehicle or capsaicin (CAP, 50 mg/kg sc) on the first and second days of life. After being weaned, male rats were assigned into four groups and treated for 2 wk with the following: vehicle + a normal sodium diet (NS, 0.4%, CON-NS), vehicle + a high-sodium diet (HS, 4%, CON-HS), CAP + NS (CAP-NS), and CAP + HS (CAP-HS). Systolic blood pressure was significantly increased in CAP-HS but not CAP-NS or CON-HS rats. Plasma and urinary 8-iso-prostaglandin F(2alpha) levels increased by approximately 40% in CON-HS and CAP-HS rats compared with their respective controls fed a NS diet (P < 0.05), and these parameters were higher in CAP-HS compared with CON-HS rats. Superoxide (O(2)(-)*) levels in the renal cortex and medulla increased by approximately 45% in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats (P < 0.05). Enhanced O(2)(-)* levels in the cortex and medulla in CAP-HS rats were prevented by preincubation of renal tissues with apocynin, a selective NAD(P)H oxidase inhibitor. Protein expression of NAD(P)H oxidase subunits, including p47(phox) and gp91(phox) in the renal cortex and medulla, was significantly increased in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats. In contrast, protein expression and activities of Cu/Zn SOD and Mn SOD were significantly increased in the renal medulla in both CAP-HS and CON-HS but in the cortex in CAP-HS rats only. Creatinine clearance decreased by approximately 45% in CAP-HS rats compared with CON-HS, CON-NS, and CAP-NS rats (P < 0.05). O(2)(-)* levels in the renal cortex of CAP-HS rats negatively correlated with creatinine clearance (r = -0.76; P < 0.001). Therefore, regardless of enhanced SOD activity to suppress oxidative stress, increased oxidative stress in the kidney of CAP-treated rats fed a HS diet is likely the result of increased expression and activities of NAD(P)H oxidase, which may contribute to decreased renal function and increased blood pressure in these rats. Our results suggest that sensory nerves may play a compensatory role in attenuating renal oxidative stress during HS intake.
Topics: Analgesics, Non-Narcotic; Animals; Animals, Newborn; Blood Pressure; Capsaicin; Dinoprost; Hypertension; Kidney; Kidney Cortex; Kidney Medulla; Male; NADP; Neurons, Afferent; Oxidative Stress; Rats; Rats, Wistar; Sodium, Dietary; Superoxide Dismutase; Superoxides
PubMed: 16920809
DOI: 10.1152/ajpheart.00529.2006 -
Journal of Veterinary Internal Medicine 2016Severe mammary tissue damage during acute coliform mastitis in cattle is partially caused by oxidative stress. Although considered a gold standard biomarker in some...
BACKGROUND
Severe mammary tissue damage during acute coliform mastitis in cattle is partially caused by oxidative stress. Although considered a gold standard biomarker in some human conditions, the utility of 15-F2t-Isoprostanes (15-F2t-Isop) in detecting oxidative stress in dairy cattle has not been validated.
HYPOTHESIS
Concentrations of 15-F2t-Isop in plasma, urine, and milk correlate with changes in oxidant status during severe coliform mastitis in cattle.
ANIMALS
Eleven lactating Holstein-Friesian dairy cows in their 3rd-6th lactation.
METHODS
A case-control study using cows with acute coliform mastitis and matched healthy controls were enrolled into this study. Measures of inflammation, oxidant status, and redox status in plasma and milk samples were quantified using commercial assays. Plasma, urine, and milk 15-F2t-Isop were quantified by liquid chromatography/tandem mass spectrometry (LC-MS/MS) and ELISA assays. Data were analyzed by Wilcoxon rank sum tests (α = 0.05).
RESULTS
Plasma 15-F2t-Isop quantified by LC-MS/MS was positively correlated with systemic oxidant status (r = 0.83; P = .01). Urine 15-F2t-Isop quantified by LC-MS/MS did not correlate with systemic oxidant status, but was negatively correlated with redox status variables (r = -0.83; P = .01). Milk 15-F2t-Isop quantified by LC-MS/MS was negatively correlated (r = -0.86; P = .007) with local oxidant status. Total 15-F2t-Isop in milk quantified by a commercial ELISA (cbELISA) was positively correlated with oxidant status in milk (r = 0.98; P < .001).
CONCLUSIONS AND CLINICAL IMPORTANCE
Free plasma 15-F2t-Isop quantified by LC-MS/MS and total milk 15-F2t-Isop quantified by cbELISA are accurate biomarkers of systemic and mammary gland oxidant status, respectively. Establishing reference intervals for free and total 15-F2t-Isops for evaluating oxidative stress in dairy cows should currently be based on the LC-MS/MS method.
Topics: Animals; Case-Control Studies; Cattle; Chromatography, Liquid; Dinoprost; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Inflammation; Lactation; Mastitis, Bovine; Milk; Oxidants; Tandem Mass Spectrometry
PubMed: 26566597
DOI: 10.1111/jvim.13793 -
Prostaglandins & Other Lipid Mediators Jan 2018Topical ocular ketorolac improves the outcomes of severe retinopathy of prematurity and when administered with systemic caffeine, decreases the severity of...
Topical ocular ketorolac improves the outcomes of severe retinopathy of prematurity and when administered with systemic caffeine, decreases the severity of oxygen-induced retinopathy. We tested the hypothesis that co-cultures of human retinal endothelial cells (HRECs) and human retinal astrocytes (HRAs) on 3-dimensional (3-D) hydrogel scaffolds is a more representative biomimetic paradigm of the blood-retinal-barrier (BRB) than 2-D cultures, and should be utilized for preclinical drug discovery and development. Mono- and co-cultures of HRECs and HRAs were treated with standard doses of ketorolac, ibuprofen, and/or caffeine, and exposed to hyperoxia, intermittent hypoxia (IH), or normoxia on 2-D surfaces or 3-D biodegradable hydrogel scaffolds (AlgiMatrix or Geltrex). Media and cells were collected at 72h post treatment for arachidonic acid metabolites. Cells cultured on 3-D scaffolds exhibited less oxidative stress and variability in drug responses. HRAs enhanced the responses of HRECs to drugs and changes in oxygen environment. PGE and PGI were the predominant prostanoids produced in response to IH, reflecting COX-2 immunoreactivity. We conclude that HRECs and HRAs co-cultured on 3-D scaffolds may recapitulate drug responses of the dynamic BRB and therefore should be implemented for preclinical ocular drug discovery and development.
Topics: Astrocytes; Biomimetics; Coculture Techniques; Cyclooxygenase 1; Cyclooxygenase 2 Inhibitors; Dinoprost; Dinoprostone; Drug Discovery; Drug Interactions; Endothelial Cells; Humans; Ibuprofen; Ketorolac; Retina; Thromboxane B2
PubMed: 28923362
DOI: 10.1016/j.prostaglandins.2017.09.005 -
Journal of Occupational and... Apr 2016A controlled human exposure study was conducted to investigate the impact of inhalational exposures to wood smoke PM2.5 on measured concentrations of airway and systemic...
OBJECTIVE
A controlled human exposure study was conducted to investigate the impact of inhalational exposures to wood smoke PM2.5 on measured concentrations of airway and systemic inflammatory biomarkers.
METHODS
Mimicking wildland firefighter activities, 10 participants were exposed to three doses of wood smoke PM2.5 (filtered-air, 250 μg/m, and 500 μg/m) while exercising on a treadmill. Exhaled breath condensate (EBC) and blood plasma samples were obtained pre-, immediately post-, and 1-hour postexposure. 8-isoprostane, pH, and myeloperoxidase were measured in EBC, while H2O2, surfactant protein D, and pentraxin-3 (PTX3) were measured in both EBC and plasma.
RESULTS
Only pH, 8-isoprostane, and PTX3 displayed significant changes when comparing pre- and postexposures.
CONCLUSIONS
Markers of inflammation and oxidative stress, including PTX3, pH, and 8-isoprostane in EBC and/or plasma, are sensitive to wood smoke inhalation, with further investigations warranted.
Topics: Biomarkers; Breath Tests; C-Reactive Protein; Dinoprost; Firefighters; Fires; Humans; Hydrogen Peroxide; Hydrogen-Ion Concentration; Inflammation; Inhalation Exposure; Male; Oxidative Stress; Particulate Matter; Peroxidase; Pulmonary Surfactant-Associated Protein D; Serum Amyloid P-Component; Smoke; Wood
PubMed: 27058482
DOI: 10.1097/JOM.0000000000000688 -
Circulation Feb 2021
Association of Cigarette and Electronic Cigarette Use Patterns With Levels of Inflammatory and Oxidative Stress Biomarkers Among US Adults: Population Assessment of Tobacco and Health Study.
Topics: Adolescent; Adult; Aged; Biomarkers; Cardiovascular Diseases; Dinoprost; Electronic Nicotine Delivery Systems; Female; Humans; Longitudinal Studies; Male; Middle Aged; Oxidative Stress; Smoking; United States; Young Adult
PubMed: 33390037
DOI: 10.1161/CIRCULATIONAHA.120.051551 -
Free Radical Biology & Medicine Jan 2019Oxidative stress has been implicated in numerous birth outcomes, including spontaneous preterm birth. However, the relationship with presentation at delivery has been...
BACKGROUND
Oxidative stress has been implicated in numerous birth outcomes, including spontaneous preterm birth. However, the relationship with presentation at delivery has been less well studied. We assessed the relationship between oxidative stress biomarkers and gestational duration with a focus on spontaneous presentation for delivery.
METHODS
Our sample included 740 women from a multi-center prospective cohort study, recruited from 2010 to 2012. Resultant measures of oxidative stress in pregnancy prostaglandin F (PGF), 8-iso-prostaglandin F (8-iso-PGF), and the primary 8-iso-PGF metabolite were measured in third trimester urine samples. Information on presentation for delivery was abstracted from medical records. We examined associations with preterm birth using adjusted logistic models. Time to event (overall delivery and spontaneous delivery) was examined using adjusted accelerated failure time models.
RESULTS
The 8-iso-PGF metabolite was associated with increased odds of overall preterm birth (OR: 1.44 [95% CI: 1.00, 2.06]), and the association with spontaneous preterm birth was similar in magnitude but not statistically significant (OR: 1.45 [95% CI: 0.96, 2.20]). We did not detect associations between other biomarkers and preterm birth, or between biomarkers and timing of overall or spontaneous delivery in accelerated failure time models.
CONCLUSIONS
Our data suggest that increased oxidative stress, as indicated by the 8-iso-PGF metabolite, may be associated with preterm birth. In contrast to previous studies, associations were similar among individuals with spontaneous versus non-spontaneous presentation for delivery.
Topics: Adult; Biomarkers; Dinoprost; Female; Humans; Infant, Newborn; Lipid Peroxidation; Oxidative Stress; Pregnancy; Pregnancy Trimester, Third; Premature Birth
PubMed: 30445128
DOI: 10.1016/j.freeradbiomed.2018.11.011 -
PloS One 2021Cardiac surgery (CS) in pediatric patients induces an overt oxidative stress (OS) response. Children are particularly vulnerable to OS related injury. The immaturity of...
INTRODUCTION
Cardiac surgery (CS) in pediatric patients induces an overt oxidative stress (OS) response. Children are particularly vulnerable to OS related injury. The immaturity of their organs and antioxidant systems as well as the induction of OS in cardio-pulmonary bypass (CPB) surgery may have an important impact on outcomes. The purpose of this study was to describe the OS response, measured by urinary free 8-iso-PGF2α, in infants undergoing CS and to evaluate the relationship between OS response and post-operative clinical outcomes.
METHODS
Infants with congenital heart disease undergoing CS with or without CPB were eligible for enrollment. Children were classified as neonates (<30 days) or infants (30 days-6 months) based on the age at surgery. Perioperative continuous non-invasive neuromonitoring included amplitude-integrated electroencephalogram and cerebral regional oxygen saturation measured with near-infrared spectroscopy. Urine 8-iso-PGF2α levels were measured before, immediately post-, and 24-hours post-surgery, and the 8-iso-PGF2 clearance was calculated.
RESULTS
Sixty-two patients (60% neonates) were included. Urine 8-iso-PGF2α levels 24 hours after surgery (8.04 [6.4-10.3] ng/mg Cr) were higher than pre-operative levels (5.7 [4.65-7.58] ng/mg Cr) (p<0.001). Those patients with a severe degree of cyanosis caused by Transposition of the Great Arteries (TGA) had the highest post-operative 8-iso-PGF2α levels. Patients with intra-operative seizures had higher post-operative 8-iso-PGF2α levels. 8-iso-PGF2α clearance at 24 hours post-surgery was different between newborns and infant patients, and it was inversely correlated with days of mechanical ventilation (p = 0.05), ICU LOS (p = 0.05) and VIS score at 24 hours (p = 0.036).
CONCLUSIONS
Children undergoing CS, particularly neonatal patients, experience a significant post-operative OS response that might play an important role in postoperative morbidity. TGA patients undergoing arterial switch operations demonstrate the highest post-operative OS response. Rapid clearance of isoprostanes, which occurs more frequently in older patients with more mature antioxidant systems, might be associated with better clinical outcomes.
Topics: Cardiac Surgical Procedures; Child; Dinoprost; Female; Humans; Infant; Infant, Newborn; Male; Oxidative Stress
PubMed: 34228731
DOI: 10.1371/journal.pone.0250124