8-isoprostane Levels Research Articles

Evaluation of Salivary 8-Isoprostane in Oral Lichen Planus: Case Control Study

Introduction: Lichen planus is a chronic inflammatory disease that affects the skin, nails, and the mucous membrane and oral mucosal involvement may frequently precedes skin manifestation. It is hypothesized that free radicals and reactive oxygen species has a strong relationship in the pathogenesis of oral lichen planus. F2-isoprostane are a group of bioactive prostaglandins and they are isomers of PGF2α is a most accurate approach to assess oxidant injury in vivo. The aim of the study was to evaluate the level of 8-isoprostane in saliva of patients with erosive and nonerosive oral lichen planus in comparison with healthy controls. Materials and Methods: The study participants were selected by convenience sampling from department of oral medicine and dermatology department of our institution. In this case control study, 36 patients with oral lichen planus and 36 control subjects were included. The lichen planus group is again subdivided into erosive and nonerosive lichen planus group. Unstimulated saliva was collected by passive drool method. The salivary 8–isoprostane level was measured by using 8-isoprostane ELISA kit. The statistical tests used were Chi square test, ANOVA and Pearson correlation. Results: The mean values of the salivary 8-isoprostane level an increase in the oral lichen planus group when compared with control group and is statistically significant (P ˂ 0.05). Conclusion: The present study showed that oxidative stress was increased in patients with oral lichen planus, reflected by higher concentration of salivary 8 isoprostane being higher in erosive lichen planus than nonerosive lichen planus.

P897 The role of oxidative stress and inflammation for stress induced left ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease patients

Abstract Background Oxidative stress and inflammation have been implicated in the pathogenesis of diastolic dysfunction (DD) and are both present in chronic obstructive pulmonary disease (COPD). Purpose To evaluate the role of oxidative stress markers (8-isoprostane) and inflammation (prostaglandin E2, resistin) in the pathogenesis of stress induced left ventricular diastolic dysfunction (LVDD) in non-severe COPD. Materials and methods 104 patients with non-severe COPD (FEV1 > 50%) and preserved left ventricular ejection fraction >50% underwent incremental cardio-pulmonary exercise testing (CPET). Echocardiography was performed before CPET and 1-2 minutes after peak exercise. Peak E/e’ ratio >15 was a marker for stress LVDD. Urine concentration of 8-isoprostanes was assumed as surrogate marker for oxidative stress; urine concentration of prostaglandine-E2 and plasma resistin levels as inflammatory markers. Mass spectrometry was applied for 8-isoprostane and prostglandine E2 (Cayman. Chemical) measurement. Values were normalised to urine creatinine (µmol/l/cre). ELISA was applied for resistin measurement (Raybio_Human) (ng/ml). Results Patients were divided into two groups: subjects with stress LVDD (67) and subjects without stress LVDD (37). 8-isoprostane levels were higher in subjects with LVDD vs those without LVDD (32.9 vs 29.67µmol/l/cre; p< 0.05). The same is observed regarding resistin plasma levels (22.51 vs 15.68ng/ml). Urine concentrations of prostaglandin E2 did not differ between the two groups (50.76 vs 51.07 µmol/l/cre) Conclusions In non-severe COPD patients the levels of oxidative stress (8-isoprostanes) and inflammation (resistin) seem to be associated with stress induced left ventricular diastolic dysfunction.

Biomarkers of Oxidative Stress in Dogs

Oxidative stress is the repair process that cells normally undergo after they metabolize oxygen and form free radicals called reactive oxygen species (ROS). When ROS production is excessive, however, cells undergo damage and release biomarker lipids and enzymes that lead to tissue inflammation, infections, obesity and cancers. This study describes a practical and rapid screening salivary test for cellular oxidative stress (OS) in dogs, which can be addressed to help enhance their health and longevity. Of the 228 dogs tested for ROS, 79 had elevated levels of the biolipid isoprostane; and 38 of them also had saliva-based profiles for food sensitivity and intolerances to 24 primary foods. Only 3 dogs were found to be reactive to 20 or more foods. These results suggest that dogs with elevated ROS and clinical issues related to intense itching, scratching, chewing, and bowel irritability had relatively few identified foods as the culprits.

P742 The role of oxidative stress and inflammation for stress induced right ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease patients

Abstract Background Oxidative stress and inflammation have been implicated in the pathogenesis of diastolic dysfunction (DD) and are both present in chronic obstructive pulmonary disease (COPD). Aim To evaluate the role of oxidative stress markers (8-isoprostane) and inflammation (prostaglandin E2, resistin) in the pathogenesis of stress induced right ventricular diastolic dysfunction (RVDD) in non-severe COPD. Materials and methods 104 patients with non-severe COPD (FEV1 > 50%) and preserved left ventricular ejection fraction >50% underwent incremental cardio-pulmonary exercise testing (CPET). Echocardiography was performed before CPET and 1-2 minutes after peak exercise. Peak E/e’ ratio > 6 was a marker for stress induced RVDD. Urine concentration of 8-isoprostanes was assumed as surrogate marker for oxidative stress; urine concentration of prostaglandine-E2 and plasma resistin levels as inflammatory markers. Mass spectrometry was applied for 8-isoprostane and prostglandine E2 (Cayman. Chemical) measurement. Values were normalised to urine creatinine (µmol/l/cre). ELISA was applied for resistin measurement (Raybio_Human) (ng/ml). Results Patients were divided into two groups: subjects with stress RVDD (82) and those without stress RVDD (22). In patients with and without RVDD the levels of 8-isoprostane were similar (30.78 vs 30.41µmol/l/cre). The urine concentration of prostaglandin E2 in patients with and without RVDD significantly differed (49.73 vs 62. 19µmol/l/cre; p < 0.05). The same is observed regarding resistin plasma levels - in patients with and without RVDD (18.91 vs 5.47ng/ml). Conclusions In non-severe COPD patients oxidative stress levels are similar in the studied groups. Inflammation (resistin) seems to be the predominant pathogenetic factor, associated with stress induced RVDD. The exact role of prostaglandine E2 for RVDD remains elusive.

The association of isoprostane levels with cardiovascular disease risk factors in Iraqi women with polycystic ovary syndrome

The association of isoprostane levels with cardiovascular disease risk factors in Iraqi women with polycystic ovary syndrome

Substance P receptor blocker, aprepitant, inhibited cutaneous and other neurogenic inflammation side effects of the EGFR1-TKI, erlotinib.

Cutaneous changes like rash and hair loss, as well as other neurogenic inflammation side effects, occur frequently during anticancer treatment with the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), erlotinib. These adverse events may be so severe that they impair the patient's compliance with the treatment or even cause its discontinuation. In the current preclinical study, rats (9.2weeks) were treated with erlotinib (10mg/kg/day) ± aprepitant (2mg/kg/day) for 12weeks. Visual changes in the development of facial skin lesions/hair loss and SP-receptor expression (immunohistochemically) in facial skin tissue were assessed; also changes in plasma magnesium, 8-isoprostane, substance P (SP), neutrophil superoxide production, and cardiac function (echocardiography) were measured. Erlotinib lowered plasma magnesium 14%, elevated SP 65%, caused 3.7-fold higher basal superoxide production, 2.5-fold higher 8-isoprostane levels, 11.6% lower cardiac systolic, and 10.9% lower diastolic function. Facial dermatological changes (alopecia, skin reddening, scabbing, nose crusting) occurred by 4weeks (± + to ++) in erlotinib-treated rats, and progressively worsened (±++ to +++) by week 12. Facial skin SP-receptor upregulation (78% higher) occurred in epidermal and hair follicle cells. All adverse effects were substantially and significantly mitigated by aprepitant, including a 62% lowering of skin SP-receptors (p < 0.05). Elevated SP levels mediated the side effects of erlotinib treatment, but aprepitant's significant prevention of the systemic and cutaneous adverse events indicates a novel potential therapy against the side effects of this anticancer treatment.

Lipid peroxidation mediated the association of urinary 1-bromopropane metabolites with plasma glucose and the risk of diabetes: A cross-sectional study of urban adults in China

Exposure to 1-bromopropane (1-BP) has been reported to cause glutathione depletion and increase the level of oxidative damage, which play critical roles in diabetes. However, the possible associations or mechanisms of the exposure of 1-BP with the plasma glucose level and the risk of diabetes are unclear. In this study, we explored the relationships of the urinary 1-BP metabolite N-Acetyl-S-(n-propyl)-l-cysteine (BPMA) with fasting plasma glucose (FPG) levels and the risk of diabetes, and the mediating role of oxidative damage in the above relationships in 3678 urban adults from the Wuhan-Zhuhai cohort in China. We found a significant dose–response relationship between BPMA and FPG levels with a β of 0.09 (95 % CI: 0.04, 0.14). In addition, mediating effect of urinary BPMA on FPG levels was observed depending on elevated 8-isoprostane level, with a median proportion of 32.06 %. Furthermore, we observed a significant association between urinary BPMA and the risk of diabetes, with an adjusted odds ratio of 1.34 (1.18, 1.52) for all participants. These results indicated that urinary 1-BP metabolites were positively associated with FPG levels and the risk of diabetes among urban adults in this cross-sectional study. Lipid peroxidation partially mediated the association between urinary 1-BP metabolites and FPG levels.

Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention.

FLT3L (Fms-like tyrosine kinase 3 ligand) stimulates the development of classical dendritic cells (DCs). Here we tested the hypothesis that classical DCs drive blood pressure elevation by promoting renal fluid retention. FLT3L-deficient (FLT3L-/-) mice that lack classical DCs in the kidney had mean arterial pressures similar to wild-types (WTs) at baseline but had blunted hypertensive responses during 4 weeks of chronic Ang II (angiotensin II) infusion. In FLT3L-/- mice, the proportions of effector memory T cells in the kidney were similar to those in WTs at baseline. However, after Ang II infusion, proportions of effector memory T cells were dramatically lower in the FLT3L-/- kidneys versus WTs, indicating that classical DCs augment the renal accumulation of effector T cells after renin-angiotensin system activation. Consistent with their lower blood pressures, the Ang II-infused FLT3L-/- mice had attenuated cardiac hypertrophy and lower renal mRNA expression for pro-hypertensive cytokines. Moreover, the Ang II-infused FLT3L-/- mice had lower urinary excretion of the oxidative stress marker 8-isoprostane and lower renal mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase 2. In an intraperitoneal saline challenge test at day 7 of Ang II, FLT3L-/- mice excreted higher proportions of the injected volume and sodium than WTs. Consistent with this enhanced diuresis, mRNA expressions for the sodium chloride cotransporter and all 3 subunits of the epithelial sodium channel were diminished by >40% in FLT3L-/- kidneys compared with the WTs. Thus, classical FLT3L-dependent DCs promote renal T-cell activation with consequent oxidative stress, fluid retention, and blood pressure elevation.

Impaired training-induced angiogenesis process with loss of pericyte-endothelium interactions is associated with an abnormal capillary remodelling in the skeletal muscle of COPD patients

Chronic obstructive pulmonary disease (COPD) is associated with exercise intolerance and limits the functional gains in response to exercise training in patients compared to sedentary healthy subjects (SHS). The blunted skeletal muscle angiogenesis previously observed in COPD patients has been linked to these limited functional improvements, but its underlying mechanisms, as well as the potential role of oxidative stress, remain poorly understood. Therefore, we compared ultrastructural indexes of angiogenic process and capillary remodelling by transmission electron microscopy in 9 COPD patients and 7 SHS after 6 weeks of individualized moderate-intensity endurance training. We also assessed oxidative stress by plasma-free and esterified isoprostane (F2-IsoP) levels in both groups. We observed a capillary basement membrane thickening in COPD patients only (p = 0.008) and abnormal variations of endothelial nucleus density in response to exercise training in these patients when compared to SHS (p = 0.042). COPD patients had significantly fewer occurrences of pericyte/endothelium interdigitations, a morphologic marker of capillary maturation, than SHS (p = 0.014), and significantly higher levels of F2-IsoP (p = 0.048). Last, the changes in pericyte/endothelium interdigitations and F2-IsoP levels in response to exercise training were negatively correlated (r = − 0.62, p = 0.025). This study is the first to show abnormal capillary remodelling and to reveal impairments during the whole process of angiogenesis (capillary creation and maturation) in COPD patients.Trial registrationNCT01183039 & NCT01183052, both registered 7 August 2010 (retrospectively registered).

Oxidative damage in mitochondrial fatty acids oxidation disorders patients and the in vitro effect of l-carnitine on DNA damage induced by the accumulated metabolites

BackgroundThe mitochondrial fatty acids oxidation disorders (FAOD) are inherited metabolic disorders (IMD) characterized by the accumulation of fatty acids of different sizes of chain according to the affected enzyme. MethodsThis study evaluated the lipid peroxidation by the measurement of 8-isoprostanes, nitrosative stress parameters by the measurement of nitrite and nitrate content and DNA and RNA oxidative damage by the measurement of oxidized guanine species in urine samples from long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and multiple acyl-CoA dehydrogenase deficiency (MADD) patients. Also, we analyzed the in vitro DNA damage by comet assay induced by adipic acid, suberic acid, hexanoylglycine and suberylglycine, separated and in combination, as well as the effect of l-carnitine in human leukocytes. ResultsAn increase on 8-isoprostanes levels in all groups of patients was observed. The nitrite and nitrate levels were increased in LCHADD patients. DNA and RNA damage evaluation revealed increase on oxidized guanine species levels in LCHADD and MADD patients. The in vitro evaluation revealed an increase on the DNA damage induced by all metabolites, besides a potencialyzed effect. l-carnitine decreased the DNA damage induced by the metabolites. ConclusionThese results demonstrate that toxic metabolites accumulated could be related to the increased oxidative and nitrosative stress of FAOD patients and that the metabolites, separated and in combination, cause DNA damage, which was reduced by l-carnitine, demonstrating antioxidant protection. General significanceThis work demonstrated oxidative stress in FAOD patients and the genotoxic potential of MCADD metabolites and the protective effect of l-carnitine.

Exposure to airborne fine particulate matter is associated with impaired endothelial function and biomarkers of oxidative stress and inflammation

Epidemiological evidence suggests that exposure to air pollution is a leading risk factor for cardiovascular disease (CVD). However, there is little direct evidence linking exposure to vascular dysfunction. We conducted a cross-sectional study of 100 participants, recruited from the University of Louisville Clinics. Endothelial function was assessed by calculating the reactive hyperemia index (RHI). Oxidative stress was indexed by measuring urinary levels of isoprostanes (n = 91). Inflammatory biomarkers were measured in the plasma (n = 80). Daily average PM2.5 levels were obtained from regional monitoring stations. Adjusted associations between PM2.5 levels and measured outcomes were tested using generalized linear models. The average age of participants was 48 years (44% male, 62% white); 52% had a diagnosis of hypertension, and 44% had type-2 diabetes. A 12.4% decrease in RHI was associated with 10 μg/m3 increase in PM2.5 (95% CI: 21.0, −2.7). The F-2 isoprostane metabolite showed a positive association of 28.4% (95% CI: 2.7, 60.3) per 10 μg/m3 increase in PM2.5. Positive associations were observed with angiopoietin 1 (17.4%; 95% CI: 2.8, 33.8), vascular endothelial growth factor (10.4%; 95% CI: 0.6, 21.0), placental growth factor (31.7%; 95% CI: 12.2, 54.5), intracellular adhesion molecule-1 (24.6%; 95% CI: 1.6, 52.8), and matrix metalloproteinase-9 (30.3%; 95% CI: 8.0, 57.5) per 10 μg/m3 increase in PM2.5. Additionally, a 10 μg/m3 increase in PM2.5 was associated with 15.9% decrease in vascular cell adhesion molecule-1 (95% CI: 28.3, −1.3). These findings suggest that exposure to PM2.5 is associated with impaired vascular function, which may result from oxidative stress and inflammation, thereby leading to a pro-atherogenic state.

Oxidatively Damaged DNA/RNA and 8-Isoprostane Levels Are Associated With the Development of Type 2 Diabetes at Older Age: Results From a Large Cohort Study.

Oxidative stress is believed to play an important role in the pathophysiology of type 2 diabetes, but the few cohort studies that have assessed the association of oxidative stress biomarkers with type 2 diabetes incidence were small and reported inconclusive results. We examined the associations of urinary oxidized guanine/guanosine (OxGua) levels (a biomarker of DNA/RNA oxidation) and urinary 8-isoprostane levels (a biomarker of lipid peroxidation) with type 2 diabetes incidence in 7,828 individuals initially without diabetes from a population-based German cohort study with 14 years of follow-up. Hazard ratios (HRs) (95% CIs) per 1 SD were obtained using multivariable-adjusted Cox proportional hazards regression models. In the total population, weak but statistically significant associations with type 2 diabetes incidence were observed for OxGua levels (HR [95% CI] per 1 SD 1.05 [1.01; 1.09]) and 8-isoprostane levels (1.04 [1.00; 1.09]). Stratified analyses showed that associations of both biomarkers with type 2 diabetes incidence were absent in the youngest age-group (50-59 years) and strongest in the oldest age-group (65-75 years) of the cohort, with HR of OxGua levels 1.14 (1.05; 1.23) per 1 SD and of 8-isoprostane levels 1.22 (1.02; 1.45) per 1 SD. These results from a large cohort study support suggestions that an imbalanced redox system contributes to the development of type 2 diabetes but suggest that this association becomes clinically apparent at older ages only, possibly as a result of reduced cellular repair capacity.

Exposure to 17 trace metals in pregnancy and associations with urinary oxidative stress biomarkers

BackgroundExposure to some toxic metals, such as lead and cadmium, has been associated with increased oxidative stress. However less is known about other metals and metal mixtures, especially in pregnant women who are a vulnerable population. MethodsTo study the relationship between exposure to trace metals and oxidative stress, we analyzed a panel of 17 metals and two oxidative stress biomarkers (8-isoprostane and 8-hydroxydeoxyguanosine [8-OHdG]) in urine samples collected at ~26 weeks gestation from pregnant women in Boston (n = 380). We used linear regression models to calculate percent differences and 95% confidence intervals (CI) in oxidative stress markers for an interquartile range (IQR) increase in each urinary metal with adjustment for other metals. In addition, we applied principal components analysis (PCA) and Bayesian kernel machine regression (BKMR), to examine cumulative effects (within correlated groups of exposures as well as overall) and interactions. ResultsWe estimated 109% (95% CI: 47, 198) higher 8-isoprostane and 71% (95% CI: 45, 102) higher 8-OHdG with an IQR increase in urinary selenium (Se). We also estimated higher 8-isoprostane (47%, 95% CI: 20.5, 79.4) and 8-OHdG (15.3%, 95% CI: 5.09, 26.5) in association with urinary copper (Cu). In our PCA, we observed higher 8-isoprostane levels in association with the “essential” PC (highly loaded by Cu, Se, and Zinc). In BKMR analyses, we also estimated higher levels of both oxidative stress biomarkers with increasing Se and Cu as well as increasing levels of both oxidative stress biomarkers in association with cumulative concentrations of urinary trace metals. ConclusionWe observed higher 8-isoprostane and 8-OHdG levels in association with urinary trace metals and elements, particularly Se and Cu, in linear models and using mixtures approaches. Additionally, increasing cumulative exposure to urinary trace metals was associated with higher levels of both oxidative stress biomarkers. The beneficial effects of these compounds should be carefully questioned.

Differential vasomotor responses to isocapnic hyperoxia: cerebral versus peripheral circulation.

Isocapnic hyperoxia (IH) evokes cerebral and peripheral hypoperfusion via both disturbance of redox homeostasis and reduction in nitric oxide (NO) bioavailability. However, it is not clear whether the magnitude of the vasomotor responses depends on the vessel network exposed to IH. To test the hypothesis that the magnitude of IH-induced reduction in peripheral blood flow (BF) may differ from the hypoperfusion response observed in the cerebral vascular network under oxygen-enriched conditions, nine healthy men (25 ± 3 yr, mean ± SD) underwent 10 min of IH during either saline or vitamin C (3 g) infusion, separately. Femoral artery (FA), internal carotid artery (ICA), and vertebral artery (VA) BF (Doppler ultrasound), as well as arterial oxidant (8-isoprostane), antioxidant [ascorbic acid (AA)], and NO bioavailability (nitrite) markers were simultaneously measured. IH increased 8-isoprostane levels and reduced nitrite levels; these responses were followed by a reduction in both FA BF and ICA BF, whereas VA BF did not change. Absolute and relative reductions in FA BF were greater than IH-induced changes in ICA and VA perfusion. Vitamin C infusion increased arterial AA levels and abolished the IH-induced increase in 8-isoprostane levels and reduction in nitrite levels. Whereas ICA and VA BF did not change during the vitamin C-IH trial, FA perfusion increased and reached similar levels to those observed during normoxia with saline infusion. Therefore, the magnitude of IH-induced reduction in femoral blood flow is greater than that observed in the vessel network of the brain, which might involve the determinant contribution that NO has in the regulation of peripheral vascular perfusion.

Urinary Biomarkers of Inflammation and Oxidative Stress Are Elevated in Obese Children and Correlate with a Marker of Endothelial Dysfunction.

Obesity is a state of chronic low-level inflammation closely associated with oxidative stress. Childhood obesity is associated with endothelial dysfunction, inflammation, and oxidative stress markers individually. This study was aimed at determining the association between the biomarkers of inflammation, oxidative stress, and endothelial dysfunction in urine samples of healthy, overweight, and obese children. Eighty-eight elementary school children aged between 6 and 10 years participated in this study. Anthropometric measurements were measured using WHO recommendations. The biomarkers of low-grade inflammation such as C-reactive protein (CRP), interleukin-6 (IL-6), and α-1-acid glycoprotein (AGP); oxidative stress markers such as 8-isoprostane and 8-hydroxy-2′-deoxyguanosine (8-OHdG); and endothelin-1 (ET-1) were analyzed in urine samples. The area under the curve (AUC) by the receiver operating characteristics (ROC) was analyzed to identify the best urinary biomarker in childhood obesity. Linear regression and Pearson correlation were analyzed to determine the association between the parameters. The obese participants have significantly increased levels of CRP, AGP, IL-6, and 8-isoprostane compared to normal-weight participants. The overweight participants had significantly increased levels of ET-1 and 8-OHdG but not the obese group compared to the NW group. The AUC for urinary CRP (AUC: 0.847, 95% CI: 0.765-0.930; p < 0.0001) and 8-isoprostane (AUC: 0.857, 95% CI: 0.783-0.932; p < 0.0001) showed a greater area under ROC curves compared to other inflammatory and oxidative markers. The urinary CRP and 8-isoprostane significantly correlated with the obesity measures (body mass index, waist circumference, and waist-to- height ratio) and ET-1, inflammatory, and oxidative markers. The increased urinary inflammatory markers and 8-isoprostane can serve as a noninvasive benchmark for early detection of the risk of developing cardiovascular disease.

Implication of Physiological and Biochemical Variables of Prognostic Importance in Lead Exposed Subjects.

The use of leaded gasoline adversely affects cardiovascular, nervous, and immune systems. Study projects to rule out different variables of prognostic importance in lead-exposed subjects. A total of 317 traffic wardens with 5years of outdoor experience and Hb levels < 10µg/dl, and 100 traffic wardens with indoor duties were substituted in two groups. Levels of vitamins, cytokines, lead, iron, minerals, oxidative stress, and lipid peroxidation were estimated with help of their standard ELISA and spectrophotometric methods respectively. The present study show increased levels of lead in subjects (29.8 ± 3.8 vs. 1.5 ± 0.2µg/dl) that may be involved in increasing oxidative stress, i.e., levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and isoprostanes were increased in subjects (4.6 ± 0.5, 4.3 ± 0.6 and 37.2 ± 5.1). Moreover, levels of antioxidants, i.e., superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), were decreased. It also exhibits reduced levels of different enzymes in anemic traffic wardens. Current study concludes that wardens exposed to environmental lead are more susceptible to develop cardiovascular and neurological disorders. It shows that toxicity of lead maybe responsible for redox imbalance and production of proinflammatory cytokines. Thus, early detection of these biomarkers may help to reduce lead toxicity and it also may help to control the dilemma of uncontrolled environmental pollution by implicating strict actions against substandard gasoline.

Long-Term Saccharin Consumption and Increased Risk of Obesity, Diabetes, Hepatic Dysfunction, and Renal Impairment in Rats.

Background and objectives: This study evaluated the effect of chronic consumption of saccharin on important physiological and biochemical parameters in rats. Materials and Methods: Male Wistar rats were used in this study and were divided into four groups: A control group and three experimental groups (groups 1, 2, and 3) were treated with different doses of saccharin at 2.5, 5, and 10 mg/kg, respectively. Each experimental group received sodium saccharin once per day for 120 days while the control group was treated with distilled water only. In addition to the evaluation of body weight, blood samples [total protein, albumin, glucose, lipid profile, alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatinine, and uric acid] and urine (isoprostane) were collected in zero time, and after 60 and 120 days for biochemical evaluation. Liver (catalase activity) and brain (8-hydroxy-2’-deoxyguanosine, 8-OHdG) tissues were collected at time zero and after 120 days. Results: The data showed that saccharin at 5 mg/kg increased body weight of treated rats after 60 (59%) and 120 (67%) days of treatment. Increased concentration of serum glucose was observed after treatment with saccharin at 5 (75% and 62%) and 10 mg/kg (43% and 40%) following 60 and 120 days, respectively. The concentration of albumin decreased after treatment with saccharin at 2.5 (34% and 36%), 5 (39% and 34%), and 10 mg/kg (15% and 21%) after 60 and 120 days of treatment, respectively. The activity of LDH and uric acid increased proportionally with dosage levels and consumption period. There was an increased concentration of creatinine after treatment with saccharin at 2.5 (125% and 68%), 5 (114% and 45%), and 10 mg/kg (26% and 31%) following 60 and 120 days, respectively. Catalase activity and 8-OHdG increased by 51% and 49%, respectively, following 120 days of treatment with saccharin at 2.5 mg/kg. Elevation in the concentration of isoprostane was observed after treatment with saccharin at all doses. Conclusions: The administration of saccharin throughout the treatment period was correlated with impaired kidney and liver function. Both hyperglycemic and obesity-inducing side effects were observed. There was an increased oxidative status of the liver, as well as exposure to increased oxidative stress demonstrated through the increased levels of isoprostane, uric acid, 8-OHdG, and activity of catalase. Therefore, it is suggested that saccharin is unsafe to be included in the diet.

The association of urinary phosphorous-containing flame retardant metabolites and oxidative stress among pregnant women in Puerto Rico

PDS 71: Exposome, Johan Friso Foyer, Floor 1, August 27, 2019, 4:30 PM - 5:30 PM Background: Phosphorous-containing flame retardants (PFRs) are frequently used as flame retardants and plasticizers. Previous research has suggested oxidative stress, the imbalance of reactive oxygen species and antioxidants, is a possible mechanism for pollutant-induced health effects. Oxidative stress measured prenatally has been associated with adverse birth outcomes including preeclampsia and preterm birth. To our knowledge, only one human study has explored associations between PFRs and oxidative stress. Methods: Pregnant women 18-40 yrs. were recruited from two hospitals and five prenatal clinics in Northern Puerto Rico (n=47) between 2011 and 2015. Concentrations of: bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), and diphenyl phosphate (DPHP) were measured in urine up to two times during pregnancy. Biomarkers for oxidative stress, 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane, were also measured in urine up to two times during pregnancy. Associations between oxidative stress biomarkers and PFRs were assessed using linear mixed models adjusted for specific gravity, age, BMI, income, and season. Results: PFR metabolites were frequently detected (≥77%). All metabolites were associated with a statistically significant increase in 8-OHdG and 8-isoprostane levels (p<0.05). BDCPP was associated with the highest increase of 8-OHdG (β=0.29; p<0.0001) while BCEtP and BCPP had the lowest increase (β=0.15; p<0.01). Similarly, BCEtP was associated with the lowest increase of 8-isoprostane levels (β=0.13; p=0.04), while BCPP was associated with the largest increase (β=0.30; p<0.0001). Conclusion: PFR metabolites were frequently detected and although our sample size was modest, our results suggest that exposure to PFRs is associated with higher levels of oxidative stress. Further investigation into these relationships and birth outcomes is warranted.

Systemic biomarkers in electronic cigarette users: implications for noninvasive assessment of vaping-associated pulmonary injuries.

BackgroundElectronic cigarettes (e-cigs) were introduced as electronic nicotine delivery systems, and have become very popular in the USA and globally. There is a paucity of data on systemic injury biomarkers of vaping in e-cig users that can be used as a noninvasive assessment of vaping-associated lung injuries. We hypothesised that characterisation of systemic biomarkers of inflammation, anti-inflammatory, oxidative stress, vascular and lipid mediators, growth factors, and extracellular matrix breakdown may provide information regarding the toxicity of vaping in e-cig users.MethodsWe collected various biological fluids, i.e. plasma, urine, saliva and exhaled breath condensate (EBC), measured pulmonary function and vaping characteristics, and assessed various biomarkers in e-cig users and nonusers.ResultsThe plasma samples of e-cig users showed a significant increase in biomarkers of inflammation (interleukin (IL)-1β, IL-6, IL-8, IL-13, interferon (IFN)-γ, matrix metalloproteinase-9, intercellular cell adhesion molecule-1) and extracellular matrix breakdown (desmosine), and decreased pro-resolving lipid mediators (resolvin D1 and resolvin D2). There was a significant increase in growth factor (endothelial growth factor, vascular endothelial growth factor, β-nerve growth factor, platelet-derived growth factor-AA, stem cell factor, hepatocyte growth factor and placental growth factor) levels in plasma of e-cig users versus nonusers. E-cig users showed a significant increase in levels of inflammatory biomarker IFN-γ, oxidative stress biomarker 8-isoprostane and oxidative DNA damage biomarker 8-oxo-dG in urine samples, and of inflammatory biomarker IL-1β in saliva samples. EBC showed a slight increase in levels of triglycerides and 8-isoprostane in e-cig users compared with normal nonusers.ConclusionE-cig users have increased levels of biomarkers of inflammation and oxidative stress, reduced pro-resolving anti-inflammatory mediators, and endothelial dysfunction, which may act as risk factors for increasing susceptibility to systemic diseases. The identified noninvasive biomarkers can be used for determining e-cig vaping-associated lung injuries, and for regulatory and diagnostic aspects of vaping in humans.

Investigating variation in urinary isoprostane levels with PM2.5

Investigating variation in urinary isoprostane levels with PM2.5