The association between diet quality indices and oxidative stress biomarkers in male footballers and healthy active controls.

OBJECTIVE: The aim of the present study was the association between the relationship between Dietary Quality Index-International (DQI-I) and Healthy Eating Index (HEI) and the urinary levels of F2alpha-isoprostane (F2a-IP) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was investigated as indicators of oxidative stress. RESULTS: Based on HEI (low, moderate, and good), the diet quality of both groups was classified as moderate. In all participants, HEI (ß=-0.29; P = 0.04) and DQI-I (ß=-0.46; P = 0.005) were inversely associated with 8-OHdG. Furthermore, a negative correlation was found between HEI (mean ß=-3.53; P = 0.04) and DQI-I (mean ß=-5.53; P = 0.004) with F2a-IP. The quality of the footballers' diet was higher than that of the control group. Following a high-quality diet, which is rich in antioxidants, is likely to effectively reduce oxidative stress.

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

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

Efficacy of Hydroxytyrosol-Rich Food Supplements on Reducing Lipid Oxidation in Humans.

In the present study we report the efficacy of two food supplements derived from olives in reducing lipid oxidation. To this end, 12 healthy volunteers received a single dose (25 mL) of olive phenolics, mainly hydroxytyrosol (HT), provided as a liquid dietary supplement (30.6 or 61.5 mg HT), followed by an investigation of two reliable markers of oxidative stress. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 h post-intake. Plasma-oxidized low-density lipoprotein (oxLDL) cholesterol levels were measured with ELISA using a monoclonal antibody, while F2-isoprostanes (F2-IsoPs) were quantified in urine with UHPLC-DAD-MS/MS. Despite the great variability observed between individuals, a tendency to reduce lipoxidation reactions was observed in the blood in response to a single intake of the food supplements. In addition, the subgroup of individuals with the highest baseline oxLDL level showed a significant (p < 0.05) decrease in F2-IsoPs at 0.5 and 12 h post-intervention. These promising results suggest that HT supplementation could be a useful aid in preventing lipoxidation. Additionally, people with a redox imbalance could benefit even more from supplementing with bioavailable HT.

Association between lipid peroxidation biomarkers and microRNA expression profiles.

BACKGROUND: In-vitro and animal studies demonstrate that epigenetic regulation may play an important role in lipid peroxidation. No human study to date has directly evaluated microRNAs (miRNAs), as epigenetic modulators, in relation to systemic levels of lipid peroxidation. OBJECTIVES: To evaluate associations between systemic levels of lipid peroxidation and miRNA expression profiles in women. METHODS: Included in the analysis were 92 women aged 40-70 years, a subset of the Shanghai Women's Health Study (SWHS). Lipid peroxidation was assessed by urinary markers F2-isoprostanes (F2-IsoPs), the products of free radical-catalyzed peroxidation of arachidonic acid, and its major metabolite after ß-oxidation, 2,3-dinor-5,6-dihydro-15-F2t-IsoP (F2-IsoP-M), with GC/NICI-MS assays. Expression levels of 798 miRNAs were quantified in peripheral plasma with NanoString nCounter assays. A multivariable linear regression model was used to examine the association between lipid peroxidation and miRNA expression. RESULTS: After adjusting for potential confounders, 29 miRNAs and 213 miRNAs were associated with F2-IsoPs and F2-IsoP-M, respectively. When further controlling for multiple comparisons, none of these nominally significant associations with F2-IsoPs was retained, whereas 71 of 213 miRNAs associated with F2-IsoP-M remained. The predicted targets of the F2-IsoP-M associated miRNAs were enriched for several lipid peroxidation-related processes such as PI3K/AKT, MAPK, FOXO and HIF-1 signaling pathways. Moreover, 10 miRNAs (miR-93-5p, miR-761, miR-301b-3p, miR-497-5p, miR-141-3p, miR-186-5p, miR-126-3p, miR-200b-3p, miR-520d-3p, and miR-363-3p) exhibited functional interactions with 50 unique mRNAs targets involved in the regulation of ß-oxidation. CONCLUSIONS: To our knowledge, this study, for the first time, provides human data suggesting that miRNA expression may be linked to lipid peroxidation products and their metabolism.

Biomarkers of Inflammation and Oxidative Stress among Adult Former Smoker, Current E-Cigarette Users-Results from Wave 1 PATH Study.

BACKGROUND: Former smokers who currently use e-cigarettes have lower concentrations of biomarkers of tobacco toxicant exposure than current smokers. It is unclear whether tobacco toxicant exposure reductions may lead to health risk reductions. METHODS: We compared inflammatory biomarkers (high-sensitivity C-reactive protein, IL6, fibrinogen, soluble intercellular adhesion molecule-1) and an oxidative stress marker (F2-isoprostane) among 3,712 adult participants in Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health Study by tobacco user groups: dual users of cigarettes and e-cigarettes; former smokers who currently use e-cigarettes-only; current cigarette-only smokers; former smokers who do not currently use any tobacco; and never tobacco users. We calculated geometric means (GM) and estimated adjusted GM ratios (GMR). RESULTS: Dual users experienced greater concentration of F2-isoprostane than current cigarette-only smokers [GMR 1.09 (95% confidence interval, CI, 1.03-1.15)]. Biomarkers were similar between former smokers who currently use e-cigarettes and both former smokers who do not use any tobacco and never tobacco users, but among these groups most biomarkers were lower than those of current cigarette-only smokers. The concentration of F2-isoprostane decreased by time since smoking cessation among both exclusive e-cigarette users (P trend = 0.03) and former smokers who do not currently use any tobacco (P trend = 0.0001). CONCLUSIONS: Dual users have greater concentration of F2-isoprostane than smokers. Exclusive e-cigarette users have biomarker concentrations that are similar to those of former smokers who do not currently use tobacco, and lower than those of exclusive cigarette smokers. IMPACT: This study contributes to an understanding of the health effects of e-cigarettes.

Urinary 8-iso PGF2α and 2,3-dinor-8-iso PGF2α can be indexes of colitis-associated colorectal cancer in mice.

Early diagnosis of colorectal cancer is needed to reduce the mortal consequence by cancer. Lipid mediators play critical role in progression of colitis and colitis-associated colon cancer (CAC) and some of their metabolites are excreted in urine. Here, we attempted to find novel biomarkers in urinary lipid metabolite of a murine model of CAC. Mice were received single administration of azoxymethane (AOM) and repeated administration of dextran sulfate sodium (DSS). Lipid metabolites in their urine was measured by liquid chromatography mass spectrometry and their colon was collected to perform morphological study. AOM and DSS caused inflammation and tumor formation in mouse colon. Liquid chromatography mass spectrometry-based comprehensive analysis of lipid metabolites showed that cyclooxygenase-mediated arachidonic acid (AA) metabolites, prostaglandins, and reactive oxygen species (ROS)-mediated AA metabolites, isoprostanes, were predominantly increased in the urine of tumor-bearing mice. Among that, urinary prostaglandin (PG)E2 metabolite tetranor-PGEM and PGD2 metabolite tetranor-PGDM were significantly increased in both of urine collected at the acute phase of colitis and the carcinogenesis phase. On the other hand, two F2 isoprostanes (F2-IsoPs), 8-iso PGF2α and 2,3-dinor-8-iso PGF2α, were significantly increased only in the carcinogenesis phase. Morphological study showed that infiltrated monocytes into tumor mass strongly expressed ROS generator NADPH (p22phox). These observations suggest that urinary 8-iso PGF2α and 2,3-dinor-8-iso PGF2α can be indexes of CAC.

Serially assessed bisphenol A and phthalate exposure and association with kidney function in children with chronic kidney disease in the US and Canada: A longitudinal cohort study.

BACKGROUND: Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD. METHODS AND FINDINGS: Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) and white (58.3%), and participants had a median age of 11.0 years (interquartile range 7.6 to 14.6) at the baseline visit. In urine samples collected serially over an average of 3.0 years (standard deviation [SD] 1.6), concentrations of BPA, phthalic acid (PA), and phthalate metabolites were measured as well as biomarkers of tubular injury (kidney injury molecule-1 [KIM-1] and neutrophil gelatinase-associated lipocalin [NGAL]) and oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and F2-isoprostane). Clinical renal function measures included estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure. Linear mixed models were fit to estimate the associations between urinary concentrations of 6 chemical exposure measures (i.e., BPA, PA, and 4 phthalate metabolite groups) and clinical renal outcomes and urinary concentrations of KIM-1, NGAL, 8-OHdG, and F2-isoprostane controlling for sex, age, race/ethnicity, glomerular status, birth weight, premature birth, angiotensin-converting enzyme inhibitor use, angiotensin receptor blocker use, BMI z-score for age and sex, and urinary creatinine. Urinary concentrations of BPA, PA, and phthalate metabolites were positively associated with urinary KIM-1, NGAL, 8-OHdG, and F2-isoprostane levels over time. For example, a 1-SD increase in ∑di-n-octyl phthalate metabolites was associated with increases in NGAL (ß = 0.13 [95% CI: 0.05, 0.21], p = 0.001), KIM-1 (ß = 0.30 [95% CI: 0.21, 0.40], p < 0.001), 8-OHdG (ß = 0.10 [95% CI: 0.06, 0.13], p < 0.001), and F2-isoprostane (ß = 0.13 [95% CI: 0.01, 0.25], p = 0.04) over time. BPA and phthalate metabolites were not associated with eGFR, proteinuria, or blood pressure, but PA was associated with lower eGFR over time. For a 1-SD increase in ln-transformed PA, there was an average decrease in eGFR of 0.38 ml/min/1.73 m2 (95% CI: -0.75, -0.01; p = 0.04). Limitations of this study included utilization of spot urine samples for exposure assessment of non-persistent compounds and lack of specific information on potential sources of exposure. CONCLUSIONS: Although BPA and phthalate metabolites were not associated with clinical renal endpoints such as eGFR or proteinuria, there was a consistent pattern of increased tubular injury and oxidative stress over time, which have been shown to affect renal function in the long term. This raises concerns about the potential for clinically significant changes in renal function in relation to exposure to common environmental toxicants at current levels.

Feline urinary F2-isoprostanes measured by enzyme-linked immunoassay and gas chromatography-mass spectroscopy are poorly correlated.

15-F2T-isoprostanes are byproducts of lipid peroxidation and were determined to be the best marker of oxidative injury in a rodent model of oxidative stress. A previous study compared methods for measurement of urinary F2-isoprostanes (gas chromatography and negative ion chemical ionization-mass spectrometry, GC-NICI-MS; and ELISA) and found poor agreement in dogs, horses, and cows. Surprisingly, fair agreement between these methods was identified in a small population of cats. We evaluated the agreement between GC-NICI-MS and ELISA of urinary F2-isoprostanes in the urine of 50 mature cats ranging from healthy to systemically ill. All urine samples had detectable levels of F2-isoprostanes by both methods. Significant proportional bias and poor agreement were identified between the 2 methods (ρ = 0.364, p = 0.009) for all cats, and in subgroup analysis based on health status. The concentration of urinary F2-isoprostanes was significantly lower in systemically ill cats compared to healthy cats when measured by ELISA (p = 0.002) but not by GC-NICI-MS (p = 0.068). Our results indicate that GC-NICI-MS and ELISA have poor agreement when measuring urinary F2-isoprostanes in cats.

dLLME-µSPE extraction coupled to HPLC-ESI-MS/MS for the determination of F2α-IsoPs in human urine.

Oxidative stress is a pathological condition characterized by an imbalance between body's antioxidant defenses and oxidizing agents, resulting in damage of endogenous molecules. These products can be used as markers of oxidative conditions; in particular, isoprostanes (IsoPs) come from the reaction of arachidonic acid with reactive oxygen species (ROS) and are currently defined as gold markers of oxidative stress in urine. Our main goal was the development of a reliable analytical method for the determination and quantification of the IsoPs in human urine by dispersive Liquid-Liquid Micro Extraction (dLLME) coupled with micro Solid Phase Extraction (µSPE) clean-up and HPLC-MS/MS analysis. The selected compounds are present in very small concentration in urine, furthermore, due to relevant matrix effect, they are challenging for ESI-MS/MS analysis. This approach provided selectivity and sensitivity for 8-isoprotaglandine F2α (8-iso-PGF2α), the "gold" OS marker, together with the main isomers. dLLME extraction allowed a significant enrichment factor and µSPE clean-up provided the removal of ion-suppressing compounds from the sample resulting in low matrix effect. The chromatographic separation was also challenging as the target compounds possess very similar chemical characteristics, so experimental conditions were carefully tuned. The reported method represents a useful tool for the detection of IsoPs in urine taking advantage of the combination of dLLME extraction and µSPE clean-up; overall recoveries were above 50 % and matrix effects were ≤15 %, with LOQs ranging between 0.020 and 0.060 ng mL-1. The procedure is easy to use and rapid allowing the removal of interfering compounds and matrix effect maintaining a highly sensitive determination.

Oxidant stress and renal function among children with chronic kidney disease: a repeated measures study.

It is hypothesized that chronic kidney disease (CKD) induces oxidant stress which contributes to the decline in kidney function. However, few studies have incorporated longitudinal designs and no studies have investigated this association among children. Using data from the Chronic Kidney Disease in Children (CKiD) study, we examined longitudinal associations between urinary biomarkers of oxidant stress, 8-OH deoxyguanosine (8-OHdG) and F2-isoprostane, and measures of renal function and blood pressure among children with CKD. Baseline levels of 8-OHdG were positively associated with estimated glomerular filtration rate (eGFR) over time and a log-unit increase in baseline 8-OHdG predicted a 5.68 ml/min/1.73 m2 increase in eGFR (95% Confidence Interval (CI): 3.75, 7.61). This association was attenuated when longitudinal measures of 8-OHdG were analyzed in relation to longitudinal eGFR (per log-unit increase in 8-OHdG, ß = 0.81, 95% CI: 0.22, 1.39). Baseline 8-OHdG concentrations were also associated with decreased proteinuria over time, as measured by urinary protein:creatinine ratio. In addition, F2-isoprostane concentrations were associated with increases in eGFR, but only when baseline levels (vs. longitudinal levels) were considered in relation to longitudinal eGFR. There were no significant associations between either 8-OHdG or F2-isoprostane and blood pressure over time. Urinary measures of oxidant stress are not associated with worsening GFR over time. Our findings suggest that excretion of these biomarkers may be influenced by changes in glomerular and tubular function in varying patterns, which would limit their value in evaluating the impact of oxidant stress on CKD progression in children.