Urinary Isoprostane Concentrations Research Articles

Oxidative Stress and Cardiovascular Risk Factors: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Introduction-Oxidative stress is linked to cardiovascular diseases (CVD) and is suggested to vary by sex. However, few population-level studies have explored these associations and the majority comprise populations with advanced CVD. We assessed urinary isoprostane concentrations, a standard measure of oxidative stress, in a relatively young and healthy cohort, hypothesizing that higher oxidative stress is associated with an adverse cardiometabolic profile and female sex. Methods-Oxidative stress was measured in 475 women and 266 men, aged 48-55 years, from the Coronary Artery Risk Development in Young Adults (CARDIA) study using urinary 8-isoprostane (IsoP) and 2,3-dinor-8-isoprostane (IsoP-M). Multivariable-adjusted regression was used to evaluate cross-sectional associations. As secondary analysis, previously measured plasma F2-isoprostanes (plasma IsoP) from another CARDIA subset was similarly analyzed. Results-Mean (SD) ages for men and women were 52.1(2.3) and 52.2(2.2) years, respectively (p = 0.46), and 39% of the participants self-identified as Black (vs. White). Before adjustments, female sex was associated with higher median urinary IsoP (880 vs. 704 ng/g creatinine in men; p < 0.01) and IsoP m (1675 vs. 1284 ng/g creatinine in men; p < 0.01). Higher body mass index (BMI), high-density cholesterol (HDL-C), and triglycerides, current smoking, and less physical activity were associated with higher oxidative stress. Diabetes was not associated with urinary IsoP but was associated with lower IsoP m and plasma IsoP. Higher serum creatinine showed diverging associations with higher plasma and lower urinary isoprostane concentrations. Conclusions-Different isoprostane entities exhibit varying association patterns with CVD risk factors, and therefore are complementary, rather than interchangeable, in assessment of oxidative stress. Still, consistently higher isoprostanes among women, smokers, less active persons, and those with higher BMI and plasma triglycerides could reflect higher oxidative stress among these groups. While urinary isoprostanes are indexed to urinary creatinine due to variations in concentration, caution should be exercised when comparing groups with differing serum creatinine.

Urinary 15-F2t-Isoprostane Concentrations in Dogs with Liver Disease.

Isoprostanes are stable end products of lipid peroxidation that can be used as markers of oxidative stress. It was previously reported that a cohort of dogs with various liver diseases had increased urinary isoprostane concentrations compared to healthy control (HC) dogs. The aim of this study was to measure and report urinary isoprostane concentrations in dogs with different types of liver diseases. Urine was collected from 21 HC dogs and from 40 dogs with liver disease, including 25 with chronic hepatitis (CH), 7 with steroid hepatopathy (SH), and 8 with a congenital portosystemic shunt (CPSS). In this prospective, observational study, urinary 15-F2t-isoprostane (F2-IsoP) concentrations were measured by liquid chromatography/mass spectrometry and normalized to urinary creatinine concentrations. Concentrations were compared between groups using a Kruskal-Wallis test followed by Dunn's multiple comparisons tests. Significance was set at p < 0.05. The median (range) urinary F2-IsoP to creatinine ratios (ng/mg UCr) were 3.6 (2.2-12.4) for HC dogs, 5.7 (2.4-11.3) for dogs with CH, 4.8 (2.4-8.6) for dogs with SH, and 12.5 (2.9-22.9) for dogs with CPSS. CPSS dogs had significantly higher urinary F2-IsoP concentrations than HC dogs (p = 0.004), suggesting increased oxidative stress among this cohort.

Impact of rs174537 on Critically Ill Patients with Acute Lung Injury: A Secondary Analysis of the OMEGA Randomized Clinical Trial.

ABSTRACTBackgroundNutrition in the intensive care unit is vital for patient care; however, immunomodulatory diets rich in PUFAs like γ-linolenic acid (GLA), EPA, and DHA remain controversial for patients with acute respiratory distress syndrome. We postulate that genetic variants impacting PUFA metabolism contribute to mixed responses to PUFA-rich diets.ObjectivesIn this study, we aimed to test the effects of single nucleotide polymorphism (SNP) rs174537 on differential responses to PUFA-rich diets.MethodsWe performed a secondary analysis of the OMEGA trial (NCT00609180) where 129 subjects received placebo control diets and 143 received omega-oil. DNA was extracted from buffy coats and used to genotype rs174537; plasma was used to quantitate PUFAs. We tested for SNP–diet interactions on PUFA concentrations, inflammatory biomarkers, and patient outcomes.ResultsWe observed that all individuals receiving omega-oil displayed significantly higher concentrations of GLA, EPA, and DHA (all P < 0.0001), but they did not vary by genotype at rs174537. Statistically significant SNP–diet interactions were observed on circulating DHA concentrations in African Americans. Specifically, African American T-allele carriers on placebo illustrated elevated DHA concentrations. Additionally, all individuals receiving omega-oil had higher concentrations of EPA-derived urinary F3-isoprostane (Caucasians: P = 0.0011; African Americans: P = 0.0002). Despite these findings, we did not detect any significant SNP–diet interactions on pulmonary functional metrics, clinical outcomes, and mortality.ConclusionsThis study highlights the importance of genetic and racial contributions to PUFA metabolism and inflammation. In particular, rs174537 had a significant impact on circulating DHA and urinary isoprostane concentrations. Given our relatively small sample size, further investigations in larger multiethnic cohorts are needed to evaluate the impact of rs174537 on fatty acid metabolism and downstream inflammation.

Urine 8-isoprostane in relation to adiposity and insulin resistance in individuals at high cardiometabolic risk.

Oxidative stress has been implicated in the pathogenesis of many conditions, including insulin resistance and obesity. However, in vivo data concerning these relationships are scarce and conflicting. Therefore, the aim of this study was to investigate the association of oxidative stress with abdominal adiposity and insulin resistance in individuals at high cardiometabolic risk. A total of 116 overweight/obese individuals participating in the HealthGrain and Etherpaths European Projects, having waist circumference (WC) and any other component of the metabolic syndrome, were included in this cross-sectional evaluation. 8-Isoprostane concentrations in 24-hr urine were measured as marker of oxidative stress in vivo. Baseline anthropometric and metabolic parameters were analyzed according to quartiles of 8-isoprostanes. Linear regression (LR) analysis was used to assess clinical correlates of oxidative stress. Urinary 8-isoprostane levels were 52% higher in men than in women (P<0.001). Across the isoprostanes quartiles, there was a significant increase in WC and body weight [P for trend<0.001; analysis of variance (ANOVA) P<0.001] and fasting triglycerides (P for trend<0.05; ANOVA P<0.05), and a significant decrease in high-density lipoprotein cholesterol (P for trend<0.001; ANOVA P=0.001). No significant association between urinary isoprostane concentrations and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] was found. WC circumference and body weight remained significant after adjustment for age and gender (P=0.023 and P=0.014, respectively) and independently associated with isoprostanes at LR (P<0.005 for both). Central obesity was independently associated with oxidative stress even in a population homogeneous for adiposity and cardiometabolic risk, whereas no relationship was observed between oxidative stress and insulin resistance.

Mycophenolate Mofetil Enhances the Negative Effects of Sirolimus and Tacrolimus on Rat Kidney Cell Metabolism

Background and PurposeMycophenolate mofetil (MMF) per se is not known to have negative effects on the kidney. MMF alone or in combination with sirolimus, can be the basis of calcineurin inhibitor (CNI)-free, kidney sparing drug protocols. However, long-term outcomes in patients on MMF/SRL seem to be inferior to those treated with regimens that include the CNI tacrolimus (TAC) due to an increased risk of allo-immune reactions. Interestingly, potential enhancement of the negative effects of SRL and TAC on the kidney by MMF has never been considered.Experimental ApproachIt was our aim to study the effects of TAC, SRL and MMF alone and evaluate their interactions when combined on the rat kidney. For this purpose we used a comprehensive molecular marker approach including measurements of urinary 8-isoprostane concentrations (oxidative stress marker) and changes of urinary metabolite patterns (1H-NMR spectroscopy) and comparing these markers to renal function (glomerular filtration rate (GFR)) and morphologic alterations (histology).Key ResultsWhile MMF alone did not impact GFR, its interaction with SRL and TAC led to a significant decrease of rats’ renal function. The decline went in parallel with a significant increase in urinary isoprostane concentrations and an enhancement of negative effects on urinary metabolite patterns.ConclusionsIn broad summary, the present study showed that MMF may enhance the negative effects of TAC on kidney function and may even display nephrotoxic properties when combined with SRL.

Airborne particulate metals in the New York City subway: A pilot study to assess the potential for health impacts

A prior study in New York City observed that airborne concentrations of three metals found in steel - iron, manganese, and chromium - are more than 100 times higher in the subway system than in aboveground air. To investigate the potential for health effects of exposure at these levels, we conducted a pilot study of subway workers comparing personal exposures to steel dust with biomarkers of metal exposure, oxidative stress, and DNA damage in blood and urine samples. Workers wore a personal air sampler operating at 4L/m for one to three work shifts with blood and urine samples collected at the end of the final shift. We found that PM(2.5) exposures varied among subway workers on the basis of job title and job activity. The subway workers' mean time-weighted PM(2.5) exposure was 52 microg/m3, with a median of 27 microg/m3, and a range of 6-469 microg/m3. The observed concentrations of PM(2.5), iron, manganese, and chromium fell well below occupational standards. Biomarker concentrations among the 39 subway workers were compared with a group of 11 bus drivers, and a group of 25 suburban office workers. Concentrations of DNA-protein crosslinks and chromium in plasma were significantly higher in subway workers than in bus drivers, but no significant difference was observed for these biomarkers between subway workers and office workers. Urinary isoprostane concentrations were significantly correlated with the number of years working in the subway system, and were detected at higher, though not significantly higher, concentrations in subway workers than in bus drivers or office workers. At the group level, there was no consistent pattern of biomarker concentrations among subway workers significantly exceeding those of the bus drivers and office workers. At the individual level, steel dust exposure was not correlated with any of the biomarkers measured.

The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function

Coronary artery bypass grafting (CABG) with cardiopulmonary bypass elicits a potent reperfusion injury and inflammatory response, more intense in patients with impaired myocardial function. Propofol has antioxidant properties which may attenuate such a response. In total, 27 patients with impaired left ventricular function undergoing CABG were randomly allocated to receive either target-controlled infusion propofol (P) or saline (S) immediately before aortic cross-clamp release until 4 h after reperfusion. Troponin-I, Urinary 8-epi PGF-2alpha isoprostane, coronary sinus and systemic malondialdehyde concentrations, Interleukin-6 (IL-6), -8 and -10 concentrations and leucocytes function studies (neutrophil respiratory burst, phagocytosis, CD-11b and CD-18 expression) were measured. Propofol decreased MDA coronary sinus concentration at 1, 3 and 5 min after reperfusion (P<0.01); 60 min after reperfusion a significant difference between the two groups in systemic MDA concentrations was also seen. IL-6 concentration increases were significantly greater in Group S than Group P, 4 h after reperfusion [1118 (1333) pg ml(-1) vs 228 (105) pg ml(-1), P<0.01]. Serum IL-8 concentrations did not increase significantly in either group. Compared with baseline values IL-10 concentrations decreased after reperfusion but the values were higher in the propofol group than in the control group [22 (16) vs 11 (4) pg ml(-1), P<0.05]. No difference in leucocyte function or urinary isoprostane concentrations was demonstrated. Propofol attenuates free-radical-mediated lipid peroxidation and systemic inflammation in patients with impaired myocardial function undergoing CABG.

Concentrations of 15F2t isoprostane in urine of dogs with intervertebral disk disease

To measure 15F(2t) isoprostane concentrations in the urine of dogs undergoing ovariohysterectomy (OHE) and dogs undergoing surgery because of intervertebral disk disease (IVDD) and to assess relationships between urinary concentrations of 15F(2t) isoprostanes and neurologic score in dogs with IVDD. 11 dogs undergoing OHE and 32 dogs with IVDD undergoing hemilaminectomy. Paired urine samples were obtained at induction of anesthesia and approximately 1 hour after OHE (controls) and were collected from dogs with IVDD at induction of anesthesia (28 samples) and approximately 1 hour after hemilaminectomy (31 samples); 26 paired urine samples were obtained from dogs with IVDD. Urinary isoprostane concentrations were measured by use of a commercial ELISA, and results were adjusted on the basis of urinary creatinine concentrations. Differences in the mean isoprostane-to-creatinine ratio were analyzed. Neurologic score was determined in dogs with IVDD by use of the modified Frankel scoring system. Urinary isoprostane-to-creatinine ratios were significantly higher in dogs with IVDD than in control dogs before and after surgery. There was no significant difference between values before and after surgery for either group. There was a significant correlation of neurologic score and urinary isoprostane-to-creatinine ratio because dogs that had higher neurologic scores (ie, less severely affected) generally had higher isoprostane-to-creatinine ratios. Urinary isoprostane-to-creatinine ratios were higher in dogs with IVDD before and after surgery. Analysis of these data suggests that dogs with IVDD are in a state of oxidative stress and that preemptive treatment with antioxidants warrants further investigation.

Urine 8-isoprostane F 2α concentrations in patients with neurogenic bladder due to spinal cord injury

Background: Isoprostanes are prostaglandin-like end products of arachidonic acid peroxidation that are produced by a free radical-catalyzed mechanism. Considering its free radical-dependent formation and potent contractor effect, it is postulated that isoprostane 8-iso PGF 2α may play an important role in oxidative stress-related smooth muscle dysfunction. These substances may also influence bladder activity directly by effects on the smooth muscle. The present study was designed to measure traditional biochemical parameters (MDA, TAS, vitamin E) in plasma and 8-iso PGF 2α concentrations in urine of patients with spinal cord injury and to evaluate the relation of urinary isoprostane concentrations to the bladder function. Methods: All spinal cord patients underwent urodynamic evaluations. The biochemical tests were performed in both hyperreflexic bladder group ( n=23) and areflexic bladder group ( n=10), and the findings were compared to those of the patients with normally functioning bladder (controls, n=19). Results: Urine 8-iso PGF 2α concentrations were significantly increased in hyperreflexic group (median value 0.89 pg/mg creatinine) compared to both control (0.52 pg/mg creatinine) and areflexic groups ( p<0.001). The lowest concentrations of urinary 8-iso PGF 2α were observed in the areflexic group (0.22 pg/mg creatinine), and these were positively correlated to the plasma MDA concentrations in areflexic patients ( p=0.05; r=0.684). Conclusion: Isoprostanes may be involved in the pathogenesis of neurogenic bladder dysfunction. It may be of value to determine the urinary concentrations of 8-iso PGF 2α in order to distinguish areflexic bladders from the hyperreflectics.