Association between F2-isoprostanes and self-reported stressors in pregnant americans of African and European ancestry.

Background: Poor birth outcomes such as preterm birth/delivery disproportionately affect African Americans compared to White individuals. Reasons for this disparity are likely multifactorial, and include prenatal psychosocial stressors, and attendant increased lipid peroxidation; however, empirical data linking psychosocial stressors during pregnancy to oxidative status are limited. Methods: We used established scales to measure five psychosocial stressors. Maternal adverse childhood experiences, financial stress, social support, anxiety, and depression were measured among 50 African American and White pregnant women enrolled in the Stress and Health in Pregnancy cohort. Liquid chromatography-tandem mass spectrometry was used to measure biomarkers of oxidative stress (four urinary F2-isoprostane isomers), to estimate oxidative status. Linear regression models were used to evaluate associations between psychosocial stressors, prenatal oxidative status and preterm birth. Results: After adjusting for maternal obesity, gestational diabetes, and cigarette smoking, African American women with higher oxidative status were more likely to report higher maternal adverse childhood experience scores (ß = 0.16, se = 1.07, p-value = 0.024) and depression scores (ß = 0.05, se = 0.02, p = 0.014). Higher oxidative status was also associated with lower gestational age at birth (ß = -0.13, se = 0.06, p = 0.04) in this population. These associations were not apparent in Whites. However, none of the cross-product terms for race/ethnicity and social stressors reached statistical significance (p > 0.05). Conclusion: While the small sample size limits inference, our novel data suggest that psychosocial stressors may contribute significantly to oxidative stress during pregnancy, and preterm birth or delivery African Americans. If replicated in larger studies, these findings would support oxidative stress reduction using established dietary or pharmacological approaches present a potential avenue to mitigate adverse effects of psychosocial stressors on birth outcomes.

Preoperative Oral Carbohydrate (CHO) Supplementation Is Beneficial for Clinical and Biochemical Outcomes in Patients Undergoing Elective Cesarean Delivery under Spinal Anaesthesia-A Randomized Controlled Trial.

BACKGROUND: Preoperative fasting and surgery cause metabolic stress, insulin resistance with ketosis, and postoperative nausea and vomiting (PONV). Oral carbohydrate loading strategy (CHO) improves outcomes in labor and general surgery. We aimed to compare the effectiveness of CHO with standard fasting in patients undergoing elective cesarean delivery (CD) under spinal anesthesia. METHODS: A single-center, parallel, prospective randomized controlled trial (RCT) was conducted in a tertiary university obstetrics department at Pomeranian Medical University in Szczecin, Poland. Patients were randomly assigned (1:1 ratio) to the CHO group (oral carbohydrate 2 h before elective CD, n = 75) or the SF group (control-standard fasting, n = 73). The main outcome measures were incidence and severity of PONV at 6 and 24 h after CD, time to the first peristalsis, time to first bowel movement, and biochemical parameters indicating ketosis in mothers and their children. RESULTS: A total of 148 adult females with singleton pregnancies undergoing elective CD under spinal anesthesia (ASA I and II) were included in the final analysis. At 24 h after CD, 8.0% from the CHO group vs. 20.55% reported three or more episodes of vomiting or dry retching as compared to patients in the SF group (p = 0.041). Preoperative CHO supplementation decreased preoperative feelings of hunger (p < 0.001) and thirst (p < 0.001). Laboratory results in the CHO group showed higher plasma pH (p = 0.001) and glucose (p < 0.001), lower F2-isoprostane in plasma (p = 0.049) and urine (p = 0.018), lower urine F2-isoprostane/creatinine ratio (p = 0.045) than in the SF group. HOMA-IR (p < 0.001) and lactate (p < 0.001) were higher in the CHO group than in the control group. CONCLUSIONS: There was no significant difference in the incidence or severity of early PONV at 6 h. The incidence of vomiting or dry retching at 24 h after cesarean delivery was lower in the CHO group as compared to standard starvation, but the combined results of PONV frequency and severity on the Wengritzky scale did not differ between the two study groups. Preoperative CHO supplementation decreased preoperative feelings of hunger and thirst, enhancing the comfort of pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04069806.

The anti-inflammatory and antioxidant effects of Montelukast on lung sepsis in adult mice.

One of the most complex clinical challenges facing medical practice is sepsis-induced lung dysfunction resulting from polymicrobial sepsis. Although many therapeutic approaches have been used in such clinical challenges, there is still further need for a new effective therapeutic approach. The objective of this study was to investigate if Montelukast could protect the lungs during polymicrobial sepsis by regulating inflammatory markers and the oxidative stress pathways. Twenty-four mature male Swiss-albino mice aged 8-12 weeks, with a weight of 20-30 g, were randomized into 4 equal groups (n=6), sham (laparotomy without cecal ligation and puncture (CLP)), CLP (laparotomy with CLP), vehicle 1 (equivalent volume of DMSO 1 hour prior to CLP), Montelukast (10 mg/kg IP 1 hour prior to CLP). Lung tissue pro-inflammatory mediators IL-6, IL-1ß, IL-17, LTB-4 12(S) HETE, and oxidative stress were assessed using ELISA. The levels of F2 isoprostane were considerably greater in the sepsis group (p<0.05) as compared to the sham group, while Montelukast was significantly lower (p<0.05) in these inflammatory mediators and oxidative stress as compared to the sepsis group. Histologically, the lung tissue damage was significant (p<0.05) in all mice in the sepsis group, while Montelukast significantly reduced lung tissue injury (p<0.05). The current findings indicated that Montelukast could attenuate lung dysfunction during CLP-induced polymicrobial sepsis in male mice through their modulating effects on pro-inflammatory and oxidative stress downstream signalling pathways and subsequently decrease lung tissue cytokine concentrations (IL-1ß, IL-6, IL-17, LTB-4, and 12(S)HETE).

LUNG PROTECTIVE POTENTIAL EFFECT OF ZILEUTON DURING ENDOTOXAEMIA MODEL IN MALE MICE.

OBJECTIVE: The aim: This study was undertaken to investigatethe possible lung protective potential effect of zileuton during polymicrobial sepsis, through modulation of inflammatory and oxidative stress pathway. PATIENTS AND METHODS: Materials and methods: 24 adult male Swiss-albino mice aged 8-12 weeks, with a weight of 25-35g, were randomized into 4 equal groups n=6, sham (laparotomy without CLP), CLP (laparotomy with CLP), vehicle (equivalent volume of DMSO 1 hour prior to CLP), and Zileuton (5 mg/kg 1 hour prior to CLP) group. After 24 hrs. of sepsis, the lung tissue harvested and used to assess IL-6, IL-1B, IL-17, LTB-4,12(S) HETE and F2-isoprostane as well as histological examination. RESULTS: Results: Lung tissue inflammatory mediators IL-6, IL-1B, IL-17, LTB, 12 (S) HETE) and oxidative stress were carried out via ELISA. Lung tissue levels of IL-6, IL-1B, IL-17, LTB4, 12(S) HETE and oxidative stress (F2 isoprostan)level were significantly higher in sepsis group (p<0.05) as compared with sham group, while zileuton combination showed significant (p<0.05) lower level in these inflammatory mediators and oxidative stress as comparedto sepsis group. Histologically, All mice in sepsis group showed a significant (p<0.05) lung tissue injury, while in zileuton pretreated group showed significantly (p<0.05) reduced lung tissue injury. CONCLUSION: Conclusions: The results of the present study revealed that zileuton has the ability to attenuate lung dysfunction during CLP induced polymicrobial sepsis in male mice through their modulating effects on LTB4,12(S) HETE and oxidative stress downstream signaling pathways and subsequently decreased lungtissue levelsof proinflammatory cytokines (IL-1ß, and IL-6,IL-17).

Impact of Dairy Intake on Plasma F2-IsoProstane Profiles in Overweight Subjects with Hyperinsulinemia: A Randomized Crossover Trial.

F2-IsoProstanes (F2-IsoPs) are major biomarkers of oxidative stress and are associated with type 2 diabetes (T2D). Further, plasma levels of F2-IsoPs may be modified by dairy products. The aim is to investigate the effect of high dairy product (HD) consumption compared to an adequate dairy product (AD) consumption on the level of F2-IsoPs among hyperinsulinemic subjects. In this crossover study, participants were randomized in two groups: HD (≥4 servings/day), or AD (≤2 servings/day) for six weeks. Fasting blood glucose and insulin were measured. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Six isomers of F2-IsoPs were quantified by HPLC-MS/MS. Twenty-seven subjects with hyperinsulinemia (mean age; 55 ± 13 years, BMI; 31.4 ± 3.3 kg/m2) were included. Fasting glucose, insulin and HOMA-IR were unchanged after HD or AD intervention. After HD intake, the total level of F2-IsoPs (p = 0.03), 5-F2t-IsoP (p = 0.002), and 8-F2t-IsoP (p = 0.004) decreased compared to AD. The 15-F2t-IsoP tended to be positively correlated with fasting blood glucose (r = 0.39, p = 0.08). Generally, F2-IsoPs levels were higher among men compared to women regardless of the dairy intake. Overall, intake of HD decreased plasma levels of F2-IsoPs compared to AD without modifying glycemic parameters.

Serum antioxidant vitamin concentrations and oxidative stress markers associated with symptoms and severity of premenstrual syndrome: a prospective cohort study.

BACKGROUND: It has been suggested that premenstrual syndrome (PMS) may derive from either elevated oxidative stress or reduced antioxidant vitamin levels in the body; however, these relationships have been minimally studied in a large cohort of healthy women. Our objective was to estimate the association between serum concentrations of antioxidant vitamins (A, C, and E) and markers of oxidative stress (F2-isoprostane) with symptoms and severity of PMS. METHODS: The BioCycle study was a prospective cohort study following 259 healthy premenopausal women aged 18-44 years for up to 2 menstrual cycles. Frequency/severity of 20 PMS symptoms were assessed via questionnaires 4 times/cycle, and antioxidant vitamins and oxidative stress biomarkers were measured up to 8 times/cycle to correspond with specific cycle phases. Generalized linear models were used to estimate associations between mean antioxidant concentrations and oxidative stress biomarkers with PMS symptoms and severity; linear mixed models were used to evaluate associations with symptom severity scores within groups (e.g. depression, cravings, pain). RESULTS: Higher concentrations of serum antioxidant vitamins were largely not associated with prevalence or severity of PMS symptoms. Though a few associations were observed, only associations between mean γ-tocopherol and decreased odds of swelling of the hands/feet survived adjustment for multiple comparisons (OR 0.33, 95% CI 0.16, 0.65, per ug/dL). However, F2-isoprostanes were associated with prevalence and severity of several symptoms specifically related to depression and cravings (depression score ß = 0.07, 95% CI 0.02, 0.12, per 10 ug/dL; cravings score ß = 0.16, 95% CI 0.10, 0.22, per 10 ug/dL), as well as with classification of PMS severity (OR 1.07, 95% CI 1.01, 1.14, per 10 pg/dL), with these associations surviving adjustment for false discovery rate. CONCLUSIONS: F2-isoprostanes, but not antioxidant vitamins, were associated with select PMS symptoms, as well as symptom and severity categories. Specific symptom relationships merit further research.

Renoprotective Potential of the Ultra-Pure Lipopolysaccharide from Rhodobacter Sphaeroides on Acutely Injured Kidneys in an Animal Model.

One of the main causes of acute kidney injury is ischemic reperfusion injury (IRI). Inflammatory response, apoptotic damages, and oxidative stress-related injuries are all involved in the pathogenesis of IRI. Toll-like receptors (TLR) are strongly associated with IRIs, especially TLR4, which is markedly induced in response to IRI. Accordingly, the current study aimed to investigate the potential renoprotective effect of ultrapure lipopolysaccharide from Rhodobacter sphaeroides (ULPS-RS) at two doses in an animal model of bilateral IRI. A total of 30 adult male rats were divided randomly into five equal groups of control (laparotomy plus bilateral renal IRI), vehicle (same as the control group, but pretreated with the vehicle), sham (laparotomy only), ULPS-RS (same as the control group, but pretreated with 0.1 mg/kg of ULPS-RS), and ULPS-RSH (same as the control group, but pretreated with 0.2 mg/kg of ULPS-RS). Subsequent to 30 min of ischemia and 2 h of reperfusion, serum samples were collected for measuring urea, creatinine, and neutrophil gelatinase-associated lipocalin. Afterward, tissue samples were obtained from all animals to measure inflammatory mediators (interleukin 6, interleukin 1ß, and tumor necrosis factor α), oxidative stress marker (8-isoprostane), apoptosis mediators (B cell lymphoma 2 [Bcl2]), and Bcl2-associated X protein (Bax). In the control group, all of the measured parameters were significantly elevated in response to IRI, except for Bcl2, which decreased significantly. On the other hand, exactly opposite effects were observed in the ULPS-RS treated groups indicating the nephroprotective effect of this compound against IRI at both tested doses. The findings reveal for the first time that ULPS-RS has the therapeutic potential of attenuating the renal dysfunction induced by IRI.

Effect of Lipopolysaccharide from Rhodobacter sphaeroides on Inflammatory Pathway and Oxidative Stress in Renal Ischemia/Reperfusion Injury in Male Rats.

Ischemia/reperfusion injury (IRI) is caused by a sudden temporary impairment of the blood flow to the particular organ. The IRI of the kidneys is one of the main causes of acute kidney injury. A vigorous inflammatory and oxidative stress response to hypoxia and reperfusion usually happens as IRI consequences that disturb the organ function. The current study aimed to investigate the effect of antagonizing toll-like receptors (TLRs) effects by lipopolysaccharide obtained from Rhodobacter sphaeroides (LPS-RS) on this critical condition. In total, 28 adult male Wistar rats were divided into four groups (n=7) as follows: the sham group which underwent only laparotomy; control group that underwent laparotomy and IRI induction; vehicle group which was similar to the control group plus vehicle treatment, LPS-RS group that was similar to the control group but was pretreated with 0.5 mg/kg of LPS-RS. The results of the current research showed that LPS-RS reduced interleukin-1ß, interleukin-6, tumor necrosis factor α, and 8-isoprostane levels, compared to the control IRI group. However, LPS-RS did not ameliorate the kidney injury as manifested by the elevated levels of urea, creatinine, and neutrophil gelatinase-associated lipocalin. Taken together, the present study demonstrated that LPS-RS at the tested dose failed to offer a renoprotective effect against the IRI in rats.

The Role of Urine F2-ISOPROSTANE CONcentration in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Haemorrhage-A Poor Prognostic Factor.

Background: The pathophysiology of delayed cerebral ischemia (DCI) remains unclear. One of the hypotheses suggests that reactive oxygen species play a role in its onset. Thus, we studied F2-isoprostanes (F2-IsoPs)-oxidative stress biomarkers. Our goal was to improve the early diagnosis of DCI in a non-invasive way. Methods: We conducted a prospective single center analysis of 38 aneurysmal subarachnoid hemorrhage patients. We assessed urine F2-IsoP concentration using immunoenzymatic arrays between the first and fifth day after bleeding. A correlation between urine F2-IsoP concentration and DCI occurrence was examined regarding clinical conditions and outcomes. Results: The urine F2-IsoP concentrations were greater than those in the control groups (p < 0.001). The 3rd day urine F2-IsoPs concentrations were correlated with DCI occurrence (p < 0.001) and long term outcomes after 12 months (p < 0.001). Conclusions: High levels of urine F2-IsoPs on day 3 can herald DCI.

Role of CAPE in reducing oxidative stress in animal models with traumatic brain injury.

INTRODUCTION: The central nervous system (CNS) is the most metabolically active organ characterized by high oxygen demand and relatively low anti-oxidative activity, which makes neurons and glia highly susceptible to damage by reactive oxygen and nitrogen byproducts as well as neurodegeneration. Free radicals are associated with secondary injuries that occur after a primary brain injury. Some of these free radical products include F2-Isoprostane (F2-IsoPs), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE) and acrolein. METHODS: In this study we measured serum F2-IsoPs levels as markers of free radical activity in 10-12 week-old male Sprague-Dawley rats weighing 200-300 g, all rats (n = 10) subjected with a head injury according to the modified marmourou model, then divided into 2 groups, one group treated with CAPE (Caffeic Acid Phenethyl Ester) (n = 5) and the other not treated with CAPE (n = 5), serum levels in the two groups were compared starting from day-0 (before brain injury), day-4 and day-7. RESULTS: We found lower F2-IsoPs levels in the group that received the CAPE treatment compared to the group that did not receive the CAPE treatment. CONCLUSION: CAPE is capable of significantly reducing oxidative stress in brain injury.

Urinary 8-isoprostane as a biomarker for oxidative stress. A systematic review and meta-analysis.

Oxidative stress is defined as an imbalance between the production and elimination of reactive oxygen species (ROS) are associated with various inflammation-related human disease. ROS can oxidize lipids, which subsequently undergo fragmentation to produce F2-isoprostanes (F2-IsoPs). Eight-isoprostane is one of the most extensively studied F2-IsoPs and the most commonly used biomarker for the assessment of oxidative stress in human studies. This urinary biomarker is quantified using either chemical or immunological techniques. A "physiological" range for 8-isoprostanes is needed to use this biomarker as a measure of excess oxidative stress originating from occupational exposures. However, ranges reported in the literature are inconsistent. We designed a standardized protocol of a systematic review and meta-analysis to assess baseline values for 8-isoprostane concentrations in urine of healthy adults and identify determinants of their inter- and intra-individual variability. We searched PubMed from journal inception and up to April 2019, and screened articles for studies containing F2-IsoPs concentrations in urine for healthy adult participants. We grouped studies in three biomarker groups: "8-isoprostane", "Isoprostanes" "15- F2t-Isoprostane". We computed geometric mean (GM) and geometric standard deviation (GSD) as the basis for the meta-analysis. Of the initial 1849 articles retrieved, 63 studies were included and 107 subgroups within these study populations were identified. We stratified the subgroups analyzed with the chemical methods by body mass index (BMI) reported. We provide pooled GM values for urinary 8-isoprostane concentrations in healthy adults, separately for chemical and immunological analysis in this review. The interquartile range (IQR) in subgroups with a mean BMI below 25 measured using chemical methods was 0.18 to 0.40 µg/g creatinine. We show that there is a significant positive association between BMI and urinary 8-isoprostane concentrations. We recommend adjusting urinary 8-isoprostane concentrations in spot urine with creatinine, quantifying 8-isoprostane with chemical analytical methods, and reporting results as median and quartiles. This will help in comparing results across studies.

8-F2-isoprostane, thioredoxin and thioredoxin reductase levels in children with obsessive-compulsive disorder.

PURPOSE: Accumulating data demonstrate that oxidative stress may play a crucial role in obsessive-compulsive disorder (OCD). This study aimed to investigate the role of 8-F2-isoprostane, thioredoxin (Trx), and thioredoxin reductase (TrxR) in children with OCD. MATERIALS AND METHODS: Thirty-three drug-free children with OCD and 35 healthy controls were included in this study. The severity of OCD symptoms was assessed via the Children's Yale Brown Obsessive-Compulsive Scale. The severity of anxiety levels was determined through the Screen for Child Anxiety-Related Emotional Disorders. Plasma levels of 8-F2-isoprostane, Trx, and TrxR were measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: Plasma 8-F2-isoprostane, Trx, and TrxR levels did not show any significant differences between patient and control groups. There were no significant correlations between plasma levels of these antioxidants and severity of OCD. CONCLUSIONS: Findings of this study did not support the involvement of oxidative stress in the etiology of childhood OCD.

Classifying oxidative stress by F2-isoprostane levels across human diseases: A meta-analysis.

The notion that oxidative stress plays a role in virtually every human disease and environmental exposure has become ingrained in everyday knowledge. However, mounting evidence regarding the lack of specificity of biomarkers traditionally used as indicators of oxidative stress in human disease and exposures now necessitates re-evaluation. To prioritize these re-evaluations, published literature was comprehensively analyzed in a meta-analysis to quantitatively classify the levels of systemic oxidative damage across human disease and in response to environmental exposures. In this meta-analysis, the F2-isoprostane, 8-iso-PGF2α, was specifically chosen as the representative marker of oxidative damage. To combine published values across measurement methods and specimens, the standardized mean differences (Hedges' g) in 8-iso-PGF2α levels between affected and control populations were calculated. The meta-analysis resulted in a classification of oxidative damage levels as measured by 8-iso-PGF2α across 50 human health outcomes and exposures from 242 distinct publications. Relatively small increases in 8-iso-PGF2α levels (g<0.8) were found in the following conditions: hypertension (g=0.4), metabolic syndrome (g=0.5), asthma (g=0.4), and tobacco smoking (g=0.7). In contrast, large increases in 8-iso-PGF2α levels were observed in pathologies of the kidney, e.g., chronic renal insufficiency (g=1.9), obstructive sleep apnoea (g=1.1), and pre-eclampsia (g=1.1), as well as respiratory tract disorders, e.g., cystic fibrosis (g=2.3). In conclusion, we have established a quantitative classification for the level of 8-iso-PGF2α generation in different human pathologies and exposures based on a comprehensive meta-analysis of published data. This analysis provides knowledge on the true involvement of oxidative damage across human health outcomes as well as utilizes past research to prioritize those conditions requiring further scrutiny on the mechanisms of biomarker generation.

Inflammatory F2-isoprostane, prostaglandin F2α, pentraxin 3 levels and breast cancer risk: The Swedish Mammography Cohort.

INTRODUCTION: Breast cancer is a common cancer among women. Identifying cellular participation of F2-isoprostane, prostaglandin F2α (PGF2α) and pentraxin 3 (PTX3) in cancer we evaluated whether their prediagnostic systemic levels that originate from different inflammatory pathways were associated with breast cancer risk. METHODS: Seventy-eight breast cancer cases diagnosed after blood collection and 797 controls from the Swedish Mammography Cohort were analysed for urinary F2-isoprostane, PGF2α and plasma PTX3 levels. RESULTS: None of the biomarkers investigated were significantly associated with breast cancer risk. However, there was the suggestion of an inverse association with PTX3 with multivariable adjusted ORs (95% CI) of 0.56 (95% CI=0.29-1.06) and 0.67 (95% CI=0.35-1.28) for the second and third tertiles, respectively (ptrend=0.20). No associations were observed between F2-isoprostane (OR=0.87; 95% CI=0.48-1.57; ptrend=0.67) and PGF2α metabolite (OR=1.03; 95% CI=0.56-1.88; ptrend=0.91) comparing the top to bottom tertiles. CONCLUSIONS: The systemic levels of F2-isoprostane, PGF2α and PTX3 witnessed in women who later developed breast cancer may not provide prognostic information regarding tumor development in spite of their known involvement in situ cellular context. These observations may indicate that other mechanisms exist in controlling cellular formation of F2-isoprostane, PGF2α and PTX3 and their systemic availability in breast cancer patients.

The relationship between plasma lipid peroxidation products and primary graft dysfunction after lung transplantation is modified by donor smoking and reperfusion hyperoxia.

BACKGROUND: Donor smoking history and higher fraction of inspired oxygen (FIO2) at reperfusion are associated with primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidative injury biomarkers would be elevated in PGD, with higher levels associated with donor exposure to cigarette smoke and recipient hyperoxia at reperfusion. METHODS: We performed a nested case-control study of 72 lung transplant recipients from the Lung Transplant Outcomes Group cohort. Using mass spectroscopy, F2-isoprostanes and isofurans were measured in plasma collected after transplantation. Cases were defined in 2 ways: grade 3 PGD present at day 2 or day 3 after reperfusion (severe PGD) or any grade 3 PGD (any PGD). RESULTS: There were 31 severe PGD cases with 41 controls and 35 any PGD cases with 37 controls. Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (28.6 pg/ml vs 19.8 pg/ml, p = 0.03). Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (29.6 pg/ml vs 19.0 pg/ml, p = 0.03) among patients reperfused with FIO2 >40%. Among recipients of lungs from donors with smoke exposure, plasma F2-isoprostane (38.2 pg/ml vs 22.5 pg/ml, p = 0.046) and isofuran (66.9 pg/ml vs 34.6 pg/ml, p = 0.046) levels were higher in severe PGD compared with control subjects. CONCLUSIONS: Plasma levels of lipid peroxidation products are higher in patients with severe PGD, in recipients of lungs from donors with smoke exposure, and in recipients exposed to higher Fio2 at reperfusion. Oxidative injury is an important mechanism of PGD and may be magnified by donor exposure to cigarette smoke and hyperoxia at reperfusion.

Are Serum Levels of F2-Isoprostane and Oxidized-LDL Related to Vitamin D Status in Type 2 Diabetic Patients? A Case-Control Study.

BACKGROUND: Considerable evidence suggests that oxidative stress affects diabetes mellitus (DM) and contributes to its complications. Vitamin D has been shown to possess antioxidant properties. The aim of this study was to determine the association between serum levels of calcifediol (25-OH-D), an indicator of vitamin D status, and lipid profiles with oxidative stress in patients with type 2 diabetes mellitus (T2DM). METHODS: In this case-control study, 57 T2DM patients with low vitamin D status (< 30 ng/mL) and 48 T2DM patients with normal vitamin D status (> 30 ng/mL) were enrolled. Fasting concentrations of 25-OH-D, calcium, phosphorus, parathyroid hormone (PTH), lipid profiles, fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), F2-isoprostane, and oxidized-low-density lipoprotein (ox-LDL) were measured. RESULTS: The mean fasting serum concentrations of 25-OH-D, calcium, and phosphorus in patients with low vitamin D status were significantly lower than in controls (p < 0.001). The mean concentrations of ox-LDL, F2-isoprostane, total cholesterol, and LDL were significantly higher in patients with low vitamin D status than in controls. There was a negative correlation between vitamin D levels and F2-isoprostane (r = 0.647and P = 0.0001), LDL (r = -0.218 and P = 0.030), and ox-LDL (r = -0.637 and P = 0.0001). CONCLUSION: The results of present study indicated that serum concentrations of 25-OH-D were inversely correlated with F2-isoprostane, LDL, and ox-LDL. Therefore, vitamin D may have a beneficial effect on the control of lipid profiles and oxidative stress in T2DM patients.

Reduction in oxidative stress biomarkers after adenotonsillectomy.

OBJECTIVES: A number of otolaryngic conditions such as chronic tonsillitis, adenoid hypertrophy, and obstructive sleep apnea are associated with oxidative stress and elevated levels of serum oxidants. The objective of this study is to measure changes in urine biomarkers of oxidative stress in children after adenotonsillectomy. METHODS: Twenty-two children with sleep disordered breathing (SDB) with tonsil and adenoid hypertrophy were enrolled prior to adenotonsillectomy. Controls consisted of 20 healthy children. Urine samples were collected from all patients. Levels of three urinary biomarkers for oxidative status, 8-hydroxy-2-deoxyguanosine (8-OxodG), F(2)-isoprostane, and malondialdehyde (MDA) were measured using high performance liquid chromatography. For the study group, urine samples were repeated 3 weeks after surgery. RESULTS: In the study group, preoperative urinary levels of 8-OxodG were higher than in controls (p=0.015). Levels decreased after surgery compared to preoperative levels (p=0.002), and reached control levels (p=0.167) at 3 weeks. Levels of urinary F(2)-isoprostane were similar in both groups (p=0.252), but decreased significantly after surgery (p=0.020). CONCLUSIONS: Children with SDB have elevated levels of urinary 8-OxodG, a marker of oxidative stress. Adenotonsillectomy results in decreased 8-OxodG and F(2)-isoprostane. These findings suggest that urine analysis may represent a valuable tool for the measurement of oxidative stress.

Habitual high intake of fatty fish is related to lower levels of F2-isoprostane in healthy women.

OBJECTIVE: The aim of this study was to determine whether habitual dietary intake of fatty fish, whole grains, fruits and vegetables, or a combination of them all, is associated with oxidative stress levels, measured as urine concentration of 8-iso-prostaglandin F2α (8-iso-PGF2α) in healthy women. METHODS: Eighty-one participants were included in this cross-sectional study. Mean age of the women was 26.1 ± 6.2 (mean ± SD) years and mean body mass index (BMI) was 22.4 ± 3.0 kg/m(2). The concentration of 8-iso-PGF2α was determined in urine, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels were determined in blood. Participants' habitual fish, whole grain, fruit, and vegetable intake was estimated from a food frequency questionnaire. RESULTS: In the multivariate analysis, there was a significant inverse association between 8-iso-PGF2α and high fatty fish intake (P < 0.001). Fatty fish intake was positively correlated to serum phospholipid concentrations of EPA (P = 0.001) and DHA (P = 0.002). A borderline effect of DHA was seen on 8-iso-PGF2α, but higher serum phospholipid concentrations of fatty acids were generally not related to lower F2-isoprostane levels. No overall effect from whole grains or fruits and vegetables was seen. CONCLUSIONS: The results indicate that high intake of fatty fish is related to lower levels of oxidative stress, but high levels of ω-3 fatty acids in intake may not alone explain the effect. High habitual intake of whole grains or fruits and vegetables did not seem to affect the F2-isoprostane level.

Levels of F2 isoprostane in Behcet's disease: Correlation with cardiometabolic risk factors.

OBJECTIVE: Behcet's disease (BD) is a chronic inflammatory disease and recent findings suggest a role of oxidative stress in the pathogenesis of BD. Free radical-induced oxidative stress is also involved in the pathogenesis of cardiovascular and other rheumatic diseases. Oxidative stress may be detected in vivo by measuring F2 isoprostanes. Here, we measured plasma levels of F2 isoprostane in patients with BD and evaluated the correlation of F2 isoprostane with cardiometabolic risk factors. METHODS: Forty-three patients with BD in remission and 37 age- and sex-matched controls were recruited for the study. Blood samples were obtained to determine F2 isoprostane, C-reactive protein levels, erythrocyte sedimentation rate, and other biochemical parameters. Homeostasis model assessment insulin resistance and body mass index were calculated. Systolic blood pressure, diastolic blood pressure, and waist circumference were measured. RESULTS: Plasma F2 isoprostane, fasting plasma glucose, triglyceride, and C-reactive protein levels were significantly higher in patients with BD compared with healthy controls, whereas high-density lipoprotein cholesterol levels were significantly lower in patients with BD. F2 isoprostane levels did not correlate with cardiometabolic risk factors, C-reactive protein levels, or erythrocyte sedimentation rate. CONCLUSION: High levels of F2 isoprostane in patients with BD indicate oxidative stress. Antioxidant therapeutic approaches could potentially affect the course of this disease.

Direct measurement of reactive oxygen species in leukocytes during hemodialysis therapy.

OBJECTIVES: Both chronic kidney disease (CKD) and hemodialysis (HD) are reported to elevate oxidative stress. Available evidence for oxidative stress is indirect measurement of oxidative stress as accumulation of byproducts by reactive oxygen species (ROS). We aimed to examine the effect of CKD and HD on ROS levels in circulating leukocytes and to compare those with conventional oxidative stress marker, F2-isoprostane, in HD patients. METHODS: Using flowcytometry techniques, ROS levels in circulating leukocytes can be directly measured in 16 HD patients and 12 healthy volunteers. We also measured circulating F2-isoprostanes levels in both groups. RESULTS: HD patients demonstrated a significant increase in serum levels of F2-isoprostanes. The direct measurement of ROS levels in leukocytes showed increase in HD patients compared to the control; 1.91-fold in polymorphonuclear leukocytes (PMN), 1.06-fold in lymphocytes, and 1.35-fold in monocytes. Significant difference between the two groups could be observed only in PMN. The ROS levels in all three fractions of leukocytes showed negative correlations with serum F2-isoprostane levels but the ROS levels only in PMN showed significant correlation (r(2) = 0.774, P = 0.001). CONCLUSIONS: Our results indicate that direct measurement of the ROS levels in circulating leukocytes by flowcytometry is a useful method to examine oxidative stress during HD procedure. The ROS levels in circulating leukocytes showed negative correlation with serum F2-isoprostane levels.