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Lahaie, Isabelle, Pierre Hardy, Xin Hou, Haroutioun Hasséssian, Pierre Asselin, Pierre Lachapelle, Guillermina Almazan et al. "A novel mechanism for vasoconstrictor action of 8-isoprostaglandin F2α on retinal vessels". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 274, n.º 5 (1 de mayo de 1998): R1406—R1416. http://dx.doi.org/10.1152/ajpregu.1998.274.5.r1406.
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Using a video-imaging technique, we characterized the effects of 8-isoprostaglandin F2α(8-iso-PGF2α) on retinal vasculature from piglets. 8-Iso-PGF2α potently contracted (EC50 = 5.9 ± 0.5 nM) retinal vessels. These effects were completely antagonized by the cyclooxygenase inhibitor indomethacin, the thromboxane synthase blocker CGS-12970, the thromboxane receptor antagonist L-670596, and the putative inhibitor of the non-voltage-dependent receptor-operated Ca2+ pathway SKF-96365; constrictor effects of 8-iso-PGF2α were also partly attenuated by the ETA-receptor blocker BQ-123 and an inhibitor of endothelin-converting enzyme, phosphoramidon, but was negligibly affected by the L-type voltage-gated Ca2+ channel blocker nifedipine. Correspondingly, 8-iso-PGF2αelicited endothelin release from retinal preparations, which was markedly reduced by SKF-96365. 8-Iso-PGF2α also increased thromboxane production in the retina and cultured endothelial cells, but not on retinovascular smooth muscle cells; these effects of 8-iso-PGF2α were blocked by indomethacin, CGS-12970, SKF-96365, and EGTA, but not by nifedipine. 8-Iso-PGF2α also increased Ca2+ transients in retinal endothelial cells, which were inhibited by SKF-96365 and EGTA, but not by nifedipine, whereas in smooth muscle cells U-46619, but not 8-iso-PGF2α, stimulated a rise in Ca2+ transients. Finally, H2O2+ FeCl2 (in vitro) and anoxia followed by reoxygenation (in vivo) stimulated formation of 8-iso-PGF2α in the retina. In conclusion, 8-iso-PGF2α-induced retinal vasoconstriction is mediated by cyclooxygenase-generated formation of thromboxane and, to a lesser extent, by endothelin after Ca2+ entry into cells, possibly through receptor-operated channels. Retinal vasoconstriction to 8-isoprostanes might play a role in the genesis of ischemic retinopathies.
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Belik, J., R. P. Jankov, J. Pan, M. Yi, C. R. Pace-Asciak y A. K. Tanswell. "Effect of 8-isoprostaglandin F2α on the newborn rat pulmonary arterial muscle and endothelium". Journal of Applied Physiology 95, n.º 5 (noviembre de 2003): 1979–85. http://dx.doi.org/10.1152/japplphysiol.00420.2003.
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8-Isoprostaglandin F2α (8-iso-PGF2α) is a bioactive lipid peroxidation product that is a vasoconstrictor at high concentrations. Paradoxically, at lower, and possibly physiological, concentrations, it is a pulmonary vascular muscle's relaxant. Its effects on newborn pulmonary vasculature are unknown. We hypothesized that the pulmonary arterial 8-iso-PGF2α responses may be developmentally regulated. Therefore, the purpose of this study was to evaluate and compare 8-iso-PGF2α effects between 1- and 2-wk-old newborn and adult rat isolated intrapulmonary arteries (100 μm) mounted on a myograph. Force after 8-iso-PGF2α stimulation was greatest in the adult ( P < 0.01). In newborns, force was significantly increased by the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) ( P < 0.01) and was suppressed by blockade of the thromboxane (Tx) A2 receptor. Whereas 8-iso-PGF2α induced a significant dose-dependent relaxation of adult precontracted vessels in the presence of a TxA2 mimetic (U-46619; 1 μM), contraction was observed in the 1-wk-old rat. This 8-iso-PGF2α-induced contraction was abolished by endothelium removal and l-NAME and was attenuated by the cyclooxygenase inhibitor ibuprofen. In the presence of a TxA2/prostaglandin H2 receptor blocker, 8-iso-PGF2α induced NO-mediated relaxation, the magnitude of which was greater in the newborn, compared with the adult ( P < 0.01). When exposed to 8-iso-PGF2α in vitro, only the newborn lung secreted TxB2. We conclude that, in contrast to its relaxant effect in the adult, 8-iso-PGF2α induces contraction of the pulmonary arteries in the early postnatal period, which is likely to be mediated by endothelium-derived TxA2. This phenomenon may contribute to the maintenance of a higher pulmonary vascular resistance in the early postnatal period.
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Sun, Ying, Yan Yan y Xuejun Kang. "Packed-Fiber Solid Phase-Extraction Coupled with HPLC-MS/MS for Rapid Determination of Lipid Oxidative Damage Biomarker 8-Iso-Prostaglandin F2α in Urine". Molecules 27, n.º 14 (10 de julio de 2022): 4417. http://dx.doi.org/10.3390/molecules27144417.
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The 8-iso-prostaglandin F2α (8-iso-PGF2α) biomarker is used as the gold standard for tracing lipid oxidative stress in vivo. The analysis of urinary 8-iso-PGF2α is challenging when dealing with trace amounts of 8-iso-PGF2α and the complexity of urine matrixes. A packed-fiber solid-phase extraction (PFSPE)–coupled with HPLC-MS/MS–method, based on polystyrene (PS)-electrospun nanofibers, was developed for the specific determination of 8-iso-PGF2α in urine and compared with other newly developed LC-MS/MS methods. The method, which simultaneously processed 12 samples within 5 min on a self-made semi-automatic array solid-phase extraction processor, was the first to introduce PS-electrospun nanofibers as an adsorbent for the extraction of 8-iso-PGF2α and was successfully applied to real urine samples. After optimizing the PFSPE conditions, good linearity in the range of 0.05–5 ng/mL with R2 > 0.9996 and a satisfactory limit of detection of 0.015 ng/mL were obtained, with good intraday and interday precision (RSD < 10%) and recoveries of 95.3–103.8%. This feasible method is expected to be used for the batch quantitative analysis of urinary 8-iso-PGF2α.
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Cabral, Pablo D., Guillermo B. Silva, Sandra T. Baigorria, Luis A. Juncos, Luis I. Juncos y Néstor H. García. "8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: role of cAMP and protein kinase A". American Journal of Physiology-Renal Physiology 299, n.º 6 (diciembre de 2010): F1396—F1400. http://dx.doi.org/10.1152/ajprenal.00225.2010.
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Salt reabsorption by the loop of Henle controls NaCl handling and blood pressure regulation. Increased oxidative stress stimulates NaCl transport in one specific segment of the loop of Henle called the thick ascending limb (TAL). The isoprostane 8-iso-prostaglandin-F2α (8-iso-PGF2α) is one of the most abundant nonenzymatic lipid oxidation products and has been implicated in the development of hypertension. However, it is not known whether 8-iso-PGF2α regulates transport or the mechanisms involved. Because protein kinase A (PKA) stimulates NaCl transport in several nephron segments, we hypothesized that 8-iso-PGF2α increases NaCl transport in the cortical TAL (cTAL) via a PKA-dependent mechanism. We examined the effect of luminal 8-iso-PGF2α on NaCl transport by measuring chloride absorption ( JCl) in isolated microperfused cTALs. Adding 8-iso-PGF2α to the lumen increased JCl by 54% (from 288.7 ± 30.6 to 446.5 ± 44.3 pmol·min−1·mm−1; P < 0.01), while adding it to the bath enhanced JCl by 35% (from 236.3 ± 35.3 to 319.2 ± 39.8 pmol·min−1·mm−1; P < 0.05). This stimulation was blocked by Na-K-2Cl cotransporter inhibition. Next, we tested the role of cAMP. Basal cAMP in the cTAL was 18.6 ± 1.6 fmol·min−1·mm−1, and 8-iso-PGF2α raised it to 35.1 ± 1.4 fmol·min−1·mm−1, an increase of 94% ( P < 0.01). Because cAMP stimulates PKA, we measured JCl using the PKA-selective inhibitor H89. In the presence of H89 (10 μM), 8-iso-PGF2α failed to increase transport regardless of whether it was added to the lumen (216.1 ± 16.7 vs. 209.7 ± 23.8 pmol·min−1·mm−1; NS) or the bath (150.4 ± 32.9 vs. 127.1 ± 28.6 pmol·min−1·mm−1; NS). We concluded that 8-iso-PGF2α stimulates cAMP and increases Cl transport in cTALs via a PKA-dependent mechanism.
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Carnevale, Roberto, Alessio Farcomeni, Roberto Cangemi, Cristina Nocella, Simona Bartimoccia, Tommasa Vicario, Mirella Saliola et al. "Serum NOX2 and urinary isoprostanes predict vascular events in patients with atrial fibrillation". Thrombosis and Haemostasis 113, n.º 03 (mayo de 2015): 617–24. http://dx.doi.org/10.1160/th14-07-0571.
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SummaryThere are limited prospective data evaluating the role of urinary F2-IsoP and NOX2 as predictive markers in atrial fibrillation (AF). The aim of this study was to analyse the role of urinary prostaglandin PGF2alpha (8-iso-PGF2α) and NOX2, markers of systemic oxidative stress, in predicting cardiovascular (CV) events and mortality in anticoagulated non-valvular AF patients. This was a prospective study including 1,002 anticoagulated AF patients, followed for a median time of 25.7 months (interquartile range: 14.8–50.9). All major CV events, CV deaths and all-cause deaths were considered as primary outcomes of the study. CV events included fatal/nonfatal ischaemic stroke, fatal/ nonfatal myocardial infarction (MI), cardiac revascularisation and transient ischaemic attack (TIA). Oxidative stress biomarkers, such as urinary 8-iso-PGF2α and serum sNOX2-dp, a marker of NOX2 activation, were measured. A CV event occurred in 125 patients (12.5 %); 78 CV deaths and 31 non-CV deaths were registered. 8-iso-PGF2α and sNOX2-dp were correlated (Rs=0.765 p> 0.001). A significant increased cumulative incidence of CV events and CV deaths was observed across tertiles for 8-iso-PGF2α and sNOX2-dp. An increased rate of all-cause death was observed across tertiles of urinary 8-iso-PGF2α.In Cox or Fine and Gray models, 8-iso-PGF2α predicted CV events and CV and non-CV deaths. The addition of tertiles of 8-iso-PGF2α to CHA2DS2-VASc score improved ROC curves for each outcome and NRI for CV events (0.24 [0.06–0.53] p=0.0067). The study shows that in AF patients 8-iso-PGF2α and NOX2 levels are predictive of CV events and total mortality. F2-IsoP may complement conventional risk factors in prediction of CV events.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief. Clinical Trial Registration: ClinicalTrials.gov NCT01882114.
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Crawford, Brittany, Dale Sandler, Hazel Nichols, Ginger Milne, Susan Steck y Yong-Moon Park. "Association Between Healthy Dietary Patterns and Markers of Oxidative Stress". Current Developments in Nutrition 6, Supplement_1 (junio de 2022): 355. http://dx.doi.org/10.1093/cdn/nzac054.010.
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Abstract Objectives Oxidative stress is involved in chronic disease etiology and the aging process and is related to antioxidant intake. However, less is known about the relationship between dietary patterns and markers of oxidative stress. We assessed cross-sectionally the association between healthy dietary patterns [alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), alternative Healthy Eating Index (aHEI), and Healthy Eating Index 2015 (HEI-2015)] and urinary F2-isoprostanes (8-iso-PGF2α and 8-iso-PGF2α-M), which are established biomarkers of oxidative stress. Methods Data were obtained from 844 premenopausal and 454 postmenopausal women participating in the Sister Study who had urinary samples analyzed for F2-isoprostanes. Responses from a 110-item validated food frequency questionnaire (FFQ) at baseline were used to calculate dietary pattern scores. Concentrations of 8-iso-PGF2α and its metabolite (8-iso-PGF2α-M) were measured by GC/MS for samples from premenopausal women and LC/MS for samples from postmenopausal women. Multivariable linear regression models were used to estimate associations between aMED, DASH, aHEI, and HEI-2015 and urinary F2-isoprostanes among pre-menopausal and post-menopausal women separately. Results Among premenopausal women, we observed significant inverse associations between the four dietary indices and mean 8-iso-PGF2α (aMED βQ4vsQ1: −0.15, 95% CI: −0.25, −0.05; DASH βQ4vsQ1: −0.15, 95% CI: −0.25, −0.25; aHEI βQ4vsQ1: −0.15, 95% CI: −0.25, −0.05; HEI-2015 βQ4vsQ1: −0.17, 95% CI: −0.27, −0.07). These associations were modified by age, education, income, and BMI, though there was no evidence of statistical interaction. In a sensitivity analysis, estimates did not substantially differ by the presence or absence of chronic disease. Among postmenopausal women, aHEI was associated with mean 8-iso-PGF2α and 8-iso-PGF2α-M (β8-iso-PGF2α: −0.003, 95% CI: −0.01, −0.005, β8-iso-PGF2α-M: −0.003, 95% CI: −0.01, −0.005). No other significant findings were observed among postmenopausal women. Conclusions Healthy dietary patterns may be associated with reduced oxidative stress, particularly among premenopausal women. Funding Sources National Institute of Environmental Health Sciences, NIH Office of Dietary Supplements, Avon Foundation, T32 from NIH-NIGMS.
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Tsikas, Dimitrios. "The dilemma of oxidative stress personified by the diprosopus 8-iso-prostaglandin F2α and prostaglandin F2α". Journal of Controversies in Biomedical Research 3, n.º 1 (28 de junio de 2017): 11–15. http://dx.doi.org/10.15586/jcbmr.2017.20.
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In general, the term “oxidative stress” describes an imbalance between oxidants and antioxidants in favor of the oxidants. While antioxidant defense is widely accepted to involve both enzymatic and non-enzymatic reactions, oxidants are generally assumed to be produced by non-enzymatic processes involving chemically produced free radicals. However, many oxidants are also formed by numerous enzymes and proteins. The F2-isoprostane 8-iso-prostaglandin F2α (8-iso-PGF2α) and malondialdehyde (MDA) are widely used as biomarkers of oxidative stress, although there is evidence that both 8-iso-PGF2α and MDA are also produced enzymatically from arachidonic acid by the action of cyclooxygenase (COX). On the contrary, there is also evidence that PGF2α is produced from arachidonic acid both by the action of COX and non-enzymatically. The duality of oxidative stress, personified by 8-iso-PGF2α and PGF2α, is a serious dilemma and demands new definitions and strategies from the scientists.
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Miyazaki, Yusuke, Tatsuro Nakamura, Shinya Takenouchi, Akane Hayashi, Keisuke Omori y Takahisa Murata. "Urinary 8-iso PGF2α and 2,3-dinor-8-iso PGF2α can be indexes of colitis-associated colorectal cancer in mice". PLOS ONE 16, n.º 1 (27 de enero de 2021): e0245292. http://dx.doi.org/10.1371/journal.pone.0245292.
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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.
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Cañizo Vázquez, Débora, Stephanie M. Hadley, Marta Pérez Ordóñez, Miriam Lopez-Abad, Anna Valls, Marta López Viñals, Bosco A. Moscoso, Sergio Benito Fernandez, Marta Camprubí-Camprubí y Joan Sanchez-de-Toledo. "Oxidative Stress and Indicators of Brain Damage Following Pediatric Heart Surgery". Antioxidants 11, n.º 3 (28 de febrero de 2022): 489. http://dx.doi.org/10.3390/antiox11030489.
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Pediatric cardiac surgery induces an increased oxidative stress (OS) response. Increased OS is associated with poor neurologic outcomes in neonatal populations with similar patterns of brain injury. We investigated OS and brain injury in infants undergoing heart surgery. Patients 6 months or younger, undergoing cardiac surgery with or without cardiopulmonary bypass (CPB), were included in this prospective, observational study. Patients were divided into infant (30 days–6 months) and neonatal (<30 days) groups for analysis. Urine OS biomarker 8-iso-prostaglandin F2α (8-iso-PGF2α) was quantified pre-surgery and at 0 and 24 h post-surgery. A serum brain damage biomarker S100B protein was also measured pre-surgery and at 0 and 72 h post-surgery. Amplitude-integrated electroencephalography during surgery was analyzed. Neuropsychological evaluation using the Bayley III or Vineland test was performed in all patients at 24 months of age. Sixty-two patients were included, 44 of whom underwent follow-up neurologic evaluation. 8-iso-PGF2α and S100B levels were increased after surgery. Postoperative levels of S100B were positively correlated with 8-iso-PGF2α levels 24 h after surgery (rho = 0.5224; p = 0.0261). There was also a correlation between immediate post-surgery levels of 8-iso-PGF2α and intra-surgery seizure burden (rho = 0.4285, p = 0.0205). Patients with an abnormal neurological evaluation had increased levels of S100B 72 h after surgery (p = 0.048). 8-iso-PGF2α levels 24 h after surgery were also related to abnormal neurologic outcomes. Levels of 8-iso-PGF2α following pediatric cardiac surgery are associated with several indicators of brain injury including brain damage biomarkers, intra-operative seizures, and abnormal neurological evaluation at follow-up, suggesting the importance of oxidative stress response in the origin of brain damage in this population.
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Petersson, Helena, Ulf Risérus, Jolene McMonagle, Hanne L. Gulseth, Audrey C. Tierney, Sophie Morange, Olfa Helal et al. "Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study". British Journal of Nutrition 104, n.º 9 (23 de junio de 2010): 1357–62. http://dx.doi.org/10.1017/s000711451000228x.
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Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P = 0·83; 15-keto-dihydro-PGF2α, P = 0·45; and CRP, P = 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.
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Richelle, M., M. E. Turini, R. Guidoux, I. Tavazzi, S. Métairon y L. B. Fay. "Gas Chromatograhy-Tandem Mass Spectrometry Determination of 8-Iso-PGF2α, a Biomarker of in vivo Lipid Peroxidation, in Human Plasma and Urine". European Journal of Mass Spectrometry 7, n.º 4-5 (agosto de 2001): 427–32. http://dx.doi.org/10.1255/ejms.453.
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The measurement of isoprostanes is a promising assay that is specific and sensitive enough to detect in vivo lipid peroxidation. We present here a gas chromatography-tandem mass spectrometry (GC/MS/MS)method that enables determination of 8-iso-prostaglandin F2α (8-iso-PGF2α)in human plasma and urine. After the addition of [2H4]-PGF2α as the internal standard to acidified plasma or urine, the samples are purified on C18 and silica cartridges, derivatised as pentafluorobenzyl esters, extracted with diethyl ether, purified on silica gel TLC plates and finally silylated. Then, 8-iso-PGF2α and its internal standard are measured by GC/MS/MS in selective-reaction monitoring mode using the transition [M −181]− to [M −181 – (3 × 90)]−. The detection limit of this method is 5 pg mL−1. Its application is presented in two situations of oxidative stress: in vitro low-density lipoprotein oxidation and in smokers. Measurement of urinary 8-iso-PGF2α levels provides a non-invasive in vivo index of free radical generation that appears not to be confounded by changes in diet.
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Hadley, Stephanie, Debora Cañizo Vazquez, Miriam Lopez Abad, Stefano Congiu, Dmytro Lushchencov, Marta Camprubí Camprubí y Joan Sanchez-de-Toledo. "Oxidative stress response in children undergoing cardiac surgery: Utility of the clearance of isoprostanes". PLOS ONE 16, n.º 7 (6 de julio de 2021): e0250124. http://dx.doi.org/10.1371/journal.pone.0250124.
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Introduction Cardiac surgery (CS) in pediatric patients induces an overt oxidative stress (OS) response. Children are particularly vulnerable to OS related injury. The immaturity of their organs and antioxidant systems as well as the induction of OS in cardio-pulmonary bypass (CPB) surgery may have an important impact on outcomes. The purpose of this study was to describe the OS response, measured by urinary free 8-iso-PGF2α, in infants undergoing CS and to evaluate the relationship between OS response and post-operative clinical outcomes. Methods Infants with congenital heart disease undergoing CS with or without CPB were eligible for enrollment. Children were classified as neonates (<30 days) or infants (30 days—6 months) based on the age at surgery. Perioperative continuous non-invasive neuromonitoring included amplitude-integrated electroencephalogram and cerebral regional oxygen saturation measured with near-infrared spectroscopy. Urine 8-iso-PGF2α levels were measured before, immediately post-, and 24-hours post-surgery, and the 8-iso-PGF2 clearance was calculated. Results Sixty-two patients (60% neonates) were included. Urine 8-iso-PGF2α levels 24 hours after surgery (8.04 [6.4–10.3] ng/mg Cr) were higher than pre-operative levels (5.7 [4.65–7.58] ng/mg Cr) (p<0.001). Those patients with a severe degree of cyanosis caused by Transposition of the Great Arteries (TGA) had the highest post-operative 8-iso-PGF2α levels. Patients with intra-operative seizures had higher post-operative 8-iso-PGF2α levels. 8-iso-PGF2α clearance at 24 hours post-surgery was different between newborns and infant patients, and it was inversely correlated with days of mechanical ventilation (p = 0.05), ICU LOS (p = 0.05) and VIS score at 24 hours (p = 0.036). Conclusions Children undergoing CS, particularly neonatal patients, experience a significant post-operative OS response that might play an important role in postoperative morbidity. TGA patients undergoing arterial switch operations demonstrate the highest post-operative OS response. Rapid clearance of isoprostanes, which occurs more frequently in older patients with more mature antioxidant systems, might be associated with better clinical outcomes.
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SMEDMAN, Annika, Bengt VESSBY y Samar BASU. "Isomer-specific effects of conjugated linoleic acid on lipid peroxidation in humans: regulation by α-tocopherol and cyclo-oxygenase-2 inhibitor". Clinical Science 106, n.º 1 (1 de enero de 2004): 67–73. http://dx.doi.org/10.1042/cs20030105.
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We have found previously that supplementation with conjugated linoleic acid (CLA) induces lipid peroxidation and inflammation in humans as indicated by an increase of 8-iso-prostaglandin F2α (PGF2α) and 15-keto-dihydro-PGF2α respectively. The present study was undertaken firstly to study the regulatory mechanisms behind these effects, and secondly to see if these effects are specific to different isomers of CLA. Sixty healthy men and women, divided into six groups, were given a cyclo-oxygenase (COX)-2 inhibitor (rofecoxib; 12 mg/day), α-tocopherol (200 mg/day) or neither treatment (control group) over a period of 6 weeks. During the last 4 weeks, three groups were given a CLA preparation (3.5 g/day) mainly containing the isomers cis-9, trans-11 and trans-10, cis-12 (CLA mix), and the three other groups a CLA preparation mainly containing the isomer trans-10, cis-12 (CLA 1012; 4.0 g/day). Treatment with α-tocopherol or COX-2 inhibitor did not alter the basal urinary levels of either 8-iso-PGF2α or 15-keto-dihydro-PGF2α. Both CLA preparations induced an increase in 8-iso-PGF2α and 15-keto-dihydro-PGF2α in the urine, with a larger increase being found in the CLA 1012 group. Treatment with the COX-2 inhibitor suppressed the increase in urinary 15-keto-dihydro-PGF2α in the CLA 1012 group, but not in the CLA mix group. Neither the COX-2 inhibitor nor α-tocopherol had any effect on 8-iso-PGF2α levels after supplementation with CLA. The CLA-induced production of PGF2α metabolites is probably partially mediated by COX-2. Levels of the induced lipid peroxidation may be dependent on the isomeric property of CLA.
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Gaino, Stefania, Valeria Zuliani, Rosa Tommasoli, Donatella Benati, Riccardo Ortolani, Carlo Zancanaro, Giorgio Berton, Clara Santonastaso y Pietro Minuz. "Functional Role of p38 Mitogen Activated Protein Kinase in Platelet Activation induced by a Thromboxane A2 Analogue and by 8-iso-prostaglandin F2 α". Thrombosis and Haemostasis 87, n.º 05 (2002): 888–98. http://dx.doi.org/10.1055/s-0037-1613101.
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SummaryWe investigated similarities in the signaling pathways elicited by the F2 isoprostane 8-iso-PGF2α and by low doses of U46619 to induce platelet activation. Both 0.01-0.1 µmol/L U46619 and 0.01-1 µmol/L 8-isoPGF2α triggered shape change and filopodia extension, as well as adhesion to immobilized fibrinogen of washed platelets. At these doses the two platelet agonists failed to trigger secretion and aggregation, which were however induced by higher doses of U46619 (0.1-1 µmol/L). SB203580 (1-10 µmol/L), a specific inhibitor of the p38 mitogen activated protein (MAP) kinase blunted platelet shape change and adhesion induced by 0.05-1 µmol/L 8-iso-PGF2α and by 0.01 µmol/L U46619. These platelet responses were also inhibited by 20 µmol/L cytochalasin D, an inhibitor of actin polymerization, and 50 µmol/L piceatannol, an inhibitor of the Syk tyrosine kinases. Both 8-iso-PGF2α and U46619-induced p38 MAP kinase phosphorylation in suspended platelets and this was inhibited by piceatannol, indicating that Syk activation occurs upstream p38 MAP kinase phosphorylation. These findings suggest that the signaling pathway triggered by both 8-iso-PGF2α and low concentrations of U46619 to induce platelet adhesion and shape change implicates Syk, the p38 MAP kinase, and actin polymerization.
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WARING, W. S., A. CONVERY, V. MISHRA, A. SHENKIN, D. J. WEBB y S. R. J. MAXWELL. "Uric acid reduces exercise-induced oxidative stress in healthy adults". Clinical Science 105, n.º 4 (1 de octubre de 2003): 425–30. http://dx.doi.org/10.1042/cs20030149.
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Uric acid (UA) possesses free-radical-scavenging properties, and systemic administration is known to increase serum antioxidant capacity. However, it is not known whether this protects against oxidative stress. The effects of raising UA concentration were studied during acute aerobic physical exercise in healthy subjects, as a model of oxidative stress characterized by increased circulating 8-iso-prostaglandin F2α (8-iso-PGF2α) concentrations. Twenty healthy subjects were recruited to a randomized double-blind placebo-controlled crossover study, and underwent systemic administration of 0.5 g of UA in 250 ml of 0.1% lithium carbonate/4% dextrose vehicle or vehicle alone as control. subjects performed high-intensity aerobic exercise for 20 min to induce oxidative stress. Plasma 8-iso-PGF2α concentrations were determined at baseline, after exercise and after recovery for 20 min. A single bout of high-intensity exercise caused a significant increase in plasma 8-iso-PGF2α concentrations from 35.0±4.7 pg/ml to 45.6±6.7 pg/ml (P<0.01). UA administration raised serum urate concentration from 293±16 to 487±16 μmol/l (P<0.001), accompanied by increased serum antioxidant capacity from 1786±39 to 1899±45 μmol/l (P<0.01). UA administration abolished the exercise-induced elevation of plasma 8-iso-PGF2α concentrations. High UA concentrations are associated with increased serum antioxidant capacity and reduced oxidative stress during acute physical exercise in healthy subjects. These findings indicate that the antioxidant properties of UA are of biological importance in vivo.
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Arogbokun, Olufunmilayo, Emma Rosen, Alexander P. Keil, Ginger L. Milne, Emily Barrett, Ruby Nguyen, Nicole R. Bush, Shanna H. Swan, Sheela Sathyanarayana y Kelly K. Ferguson. "Maternal Oxidative Stress Biomarkers in Pregnancy and Child Growth from Birth to Age 6". Journal of Clinical Endocrinology & Metabolism 106, n.º 5 (1 de febrero de 2021): 1427–36. http://dx.doi.org/10.1210/clinem/dgab018.
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Abstract Context Maternal oxidative stress in pregnancy can arise through a multitude of sources and may have lifelong consequences for the child. Animal studies suggest that prenatal oxidative stress may contribute to metabolic dysfunction and excessive weight gain in the offspring. However, this relationship has been studied minimally in humans. Objective Determine the association between prenatal oxidative stress biomarkers and child weight and body mass index (BMI) z-scores from birth to age 6. Methods Within The Infant Development and the Environment Study (TIDES) prospective pregnancy cohort, we calculated age- and sex-specific Z-scores for child weight and BMI, measured between birth and age 6 (N = 736). Three oxidative stress biomarkers were quantified in third-trimester urine, including 8-iso-prostaglandin F2α (8-iso-PGF2α), its primary metabolite, and prostaglandin F2α (PGF2α). We examined associations between each biomarker and Z-scores using linear regression as well as group-based trajectory modeling. Results Prenatal 8-iso-PGF2α and its metabolite were associated with lower birth weight and higher weight at age 4. For example, an ln-unit increase in 8-iso-PGF2α was associated with 0.17 SD higher weight at age 4 (95% CI 0.01, 0.33). These biomarkers were also associated with higher BMI at age 4. Finally, within 4 unique weight trajectories (low, normal, high, and low–high), children of mothers with higher 8-iso-PGF2α were 2.56 times more likely (95% CI 1.22, 5.41) to be in the low–high trajectory than children in the normal group. Conclusion We observed associations between third-trimester oxidative stress and lower birth weight as well as higher early childhood weight and BMI. These findings have important implications for understanding the developmental origins of childhood weight gain and metabolic disease.
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Loffredo, Lorenzo, Evaristo Ettorre, Anna Maria Zicari, Maurizio Inghilleri, Cristina Nocella, Ludovica Perri, Alberto Spalice et al. "Oxidative Stress and Gut-Derived Lipopolysaccharides in Neurodegenerative Disease: Role of NOX2". Oxidative Medicine and Cellular Longevity 2020 (1 de febrero de 2020): 1–7. http://dx.doi.org/10.1155/2020/8630275.
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Background. Neurodegenerative diseases (ND) as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis represent a growing cause of disability in the developed countries. The underlying physiopathology is still unclear. Several lines of evidence suggest a role for oxidative stress and NADPH oxidase 2 (NOX2) in the neuropathological pathways that lead to ND. Furthermore, recent studies hypothesized a role for gut microbiota in the neuroinflammation; in particular, lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut is believed to play a role in causing ND by increase of oxidative stress and inflammation. The aim of this study was to assess NOX2 activity as well as serum 8-iso-prostaglandin F2α (8-iso-PGF2α), serum H2O2, and LPS in patients with ND compared to controls. Methods. One hundred and twenty-eight consecutive subjects, including 64 ND patients and 64 controls (CT) matched for age and gender, were recruited. A cross-sectional study was performed to compare serum activity of soluble NOX2-dp (sNOX2-dp), blood levels of isoprostanes, serum H2O2, and LPS in these two groups. Serum zonulin was used to assess gut permeability. Results. Compared with CT, ND patients had higher values of sNOX2-dp, 8-iso-PGF2α, H2O2, and LPS. Simple linear regression analysis showed that sNOX2-dp was significantly correlated with serum LPS (Rs=0.441; p<0.001), zonulin (Rs=0.411; p<0.001), serum H2O2 (Rs=0.329; p<0.001), and 8-iso-PGF2α (Rs=0.244; p=0.006). LPS significantly correlated with serum zonulin (Rs=0.818; p<0.001) and 8-iso-PGF2α (Rs=0.280; p=0.001). A multiple linear regression analysis was performed to define the independent predictors of sNOX2-dp. LPS (SE, 0.165; standardized coefficient β, 0.459; p<0.001) and 8-iso-PGF2α (SE, 0.018; standardized coefficient β, 0.220; p=0.005) emerged as the only independent predictive variables associated with sNOX2-dp (R2=57%). Conclusion. This study provides the first report attesting that patients with ND have high NOX2 activation that could be potentially implicated in the process of neuroinflammation.
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Dietrich, Stefan, Anna-Liisa Elorinne, Nick Bergau, Klaus Abraham, Tilman Grune, Juha Laakso, Daniela Weber, Cornelia Weikert y Bernhard H. Monien. "Comparison of Five Oxidative Stress Biomarkers in Vegans and Omnivores from Germany and Finland". Nutrients 14, n.º 14 (16 de julio de 2022): 2918. http://dx.doi.org/10.3390/nu14142918.
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When the amount of reactive oxygen species produced by human metabolism cannot be balanced by antioxidants, this phenomenon is commonly referred to as oxidative stress. It is hypothesised that diets with high amounts of plant food products may have a beneficial impact on oxidative stress status. However, few studies have examined whether a vegan diet is associated with lower oxidative stress compared to an omnivorous diet. The present cross-sectional study aimed to compare the levels of five oxidative stress biomarkers in vegans and omnivores. Data of 36 vegans and 36 omnivores from Germany and of 21 vegans and 18 omnivores from Finland were analysed. HPLC coupled with mass spectrometry or fluorescence detection and ELISA methods were used to measure the oxidative stress biomarkers malondialdehyde (MDA), protein carbonyls and 3-nitrotyrosine in plasma and 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in 24 h urine. Analyses of variance and covariance, considering potential confounders, were used. Vegans and omnivores showed no differences in MDA and protein carbonyl concentrations. In Finnish but not in German vegans, the concentrations of 3-nitrotyrosine were lower compared to those in omnivores (p = 0.047). In Germany, vegans showed lower excretion levels of 8-iso-PGF2α than omnivores (p = 0.002) and with a trend also of 8-OHdG (p = 0.05). The sensitivity analysis suggests lower 8-iso-PGF2α excretion levels in women compared to men, independently of the dietary group. The present study contributes to expanding our knowledge of the relationship between diet and oxidative stress and showed that 3-nitrotyrosine, 8-OHdG and 8-iso-PGF2α tended to be lower in vegans. Furthermore, studies are recommended to validate the present findings.
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Takebayashi, Kohzo, Sachiko Matsumoto, Yoshimasa Aso y Toshihiko Inukai. "Aldosterone Blockade Attenuates Urinary Monocyte Chemoattractant Protein-1 and Oxidative Stress in Patients with Type 2 Diabetes Complicated by Diabetic Nephropathy". Journal of Clinical Endocrinology & Metabolism 91, n.º 6 (1 de junio de 2006): 2214–17. http://dx.doi.org/10.1210/jc.2005-1718.
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Abstract Context: Aldosterone causes organic impairment by enhancement of oxidative stress and subsequent induction of proinflammatory cytokines and chemokines. Objective: This study was designed to investigate the effect of spironolactone, an aldosterone blocker, on oxidative stress and the level of urinary monocyte chemoattractant protein (MCP)-1, a cysteine-cysteine chemokine that may contribute to progression of various nephropathies in type 2 diabetic patients with diabetic nephropathy. Design, Setting, Patients and Other Participants, and Intervention: The patients were randomly assigned to two groups in which they received either spironolactone (50 mg/d; n = 23) or amlodipine (2.5 mg/d; n = 14). Main Outcome Measures: Urinary 8-iso-prostaglandin (PG) F2α (a marker of oxidative stress), urinary MCP-1, and urinary albumin excretion (UAE) were measured at the start of administration (0 months) and after 3 months in each group. Baseline levels of these variables were also measured in 25 age-matched healthy subjects. Results: There were significant positive correlations between log10-transformed (log) 8-iso-PGF2α and log MCP-1 levels in control and diabetic subjects and all subjects combined, but no correlations between log UAE and log 8-iso-PGF2α or log MCP-1 were found in any group. Significant decreases in 8-iso-PGF2α, MCP-1, and UAE were observed with spironolactone (P = 0.0001, P = 0.0041, and P = 0.0037, respectively), and systolic blood pressure significantly decreased after both spironolactone and amlodipine therapy (P = 0.00011 and P = 0.0051, respectively). Conclusions: Our data suggest that urinary MCP-1 is correlated with oxidative stress as measured by urinary 8-iso-PGF2α and that spironolactone can decrease urinary MCP-1 and oxidative stress.
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Recinella, Lucia, Annalisa Chiavaroli, Giustino Orlando, Luigi Menghini, Claudio Ferrante, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Luigi Brunetti y Sheila Leone. "Protective Effects Induced by Two Polyphenolic Liquid Complexes from Olive (Olea europaea, mainly Cultivar Coratina) Pressing Juice in Rat Isolated Tissues Challenged with LPS". Molecules 24, n.º 16 (19 de agosto de 2019): 3002. http://dx.doi.org/10.3390/molecules24163002.
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MOMAST(®) HY100 and MOMAST(®) HP30 are polyphenolic liquid complexes from olive pressing juice with a total polyphenolic content of 100 g/kg (at least 50% as hydroxytyrosol) and 36 g/kg (at least 30% as hydroxytyrosol), respectively. We investigated the potential protective role of MOMAST(®) HY100 and MOMAST(®) HP30 on isolated rat colon, liver, heart, and prefrontal cortex specimens treated with Escherichia coli lipopolysaccharide (LPS), a validated ex vivo model of inflammation, by measuring the production of prostaglandin (PG)E2, 8-iso-PGF2α, lactate dehydrogenase (LDH), as well as cyclooxygenase (COX)-2, tumor necrosis factor α (TNFα), and inducible nitric oxide synthase (iNOS) mRNA levels. MOMAST(®) HY100 decreased LPS-stimulated PGE2 and LDH levels in all tested tissues. Following treatment with MOMAST(®) HY100, we found a significant reduction in iNOS levels in prefrontal cortex and heart specimens, COX-2 and TNFα mRNA levels in heart specimens, and 8-iso-PGF2α levels in liver specimens. On the other hand, MOMAST(®) HP30 was found to blunt COX-2, TNFα, and iNOS mRNA levels, as well as 8-iso-PGF2α in cortex, liver, and colon specimens. MOMAST(®) HP30 was also found to decrease PGE2 levels in liver specimens, while it decreased iNOS mRNA, LDH, and 8-iso-PGF2α levels in heart specimens. Both MOMAST(®) HY100 and MOMAST(®) HP30 exhibited protective effects on multiple inflammatory and oxidative stress pathways.
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Ashcheulova, T. V., N. N. Gerasimchuk, O. N. Kovalyova, K. N. Kompaniiets y O. V. Honchar. "Effects of antihypertensive treatment on systemic inflammation, oxidative stress and proinflammatory cytokine levels". Regulatory Mechanisms in Biosystems 11, n.º 4 (11 de noviembre de 2020): 536–41. http://dx.doi.org/10.15421/022082.
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Hypertension in its origin is a heterogeneous and multisystemic disease. Evaluation of oxidative stress activity based on the level of 8-iso-PgF2α, proinflammatory activity based on tumour necrosis factor-α, its type I soluble receptor, and C-reactive protein levels is relevant for further understanding of pathogenesis of hypertension and improvement of the early diagnostics of heart failure. 186 hypertensive patients were observed during a 2-months course of treatment, aged 30 to 65 years. Serum levels of 8-iso-PgF2α (n = 34), tumour necrosis factor-α and its type I soluble receptor were determined by ELISA before and after course of treatment. C-reactive protein level was determined by biochemical method. The control group included 16 clinically healthy individuals, aged 27 to 55 years. Hypertensive patients enrolled into the study were randomized into three groups that received different protocols of combined anti-hypertensive therapy: I clinical group – а combination of bisoprolol and indapamid, II – а combination of lacidipine and candesartan, III – а combination of fosinopril sodium and hydrochlorothiazide. On the background of combined antihypertensive therapy, we observed favourable dynamics of 8-iso-PgF2α, tumour necrosis factor-α and its type I soluble receptor, and C-reactive protein levels. Taking into account the insignificance of the correlations revealed, a one-factor dispersion analysis was applied which allowed us to determine the influence of the grade and duration of hypertension on the dynamics of the studied parameters. It has been found that the grade of hypertension is related to an increase in TNF-α and 8-iso-PgF2α serum levels, but not in TNF-α type I soluble receptor, and the duration of hypertension is related to an increase in C-reactive protein, TNF-α and its type I soluble receptor levels, with no relation to the level of 8-iso-PgF2α. Thus, oxidative stress possibly promotes the activation of potentially damaging immune mechanisms mediated by proinflammatory cytokines, nonspecific inflammation and drives the further progression of lesions in the target organs.
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Vacchiano, Charles A., George R. Osborne y George E. Tempel. "8-ISO-PGF2α PRODUCTION BY ALVEOLAR MACROPHAGES EXPOSED TO HYPEROXIA". Shock 9, n.º 4 (abril de 1998): 266–73. http://dx.doi.org/10.1097/00024382-199804000-00006.
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Dragani, Alfredo, Angela Falco, Francesca Santilli, Stefania Basili, Giancarlo Rolandi, Loredana Cerasa, Stefano Lattanzio, Giovanni Ciabattoni, Carlo Patrono y Giovanni Davì. "Oxidative stress and platelet activation in subjects with moderate hyperhomocysteinaemia due to MTHFR 677 C→T polymorphism". Thrombosis and Haemostasis 108, n.º 09 (2012): 533–42. http://dx.doi.org/10.1160/th11-12-0899.
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SummaryThe methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C→T polymorphism and in non-carriers, in relation to tHcy and folate levels. A cross-sectional comparison of urinary 8-iso-prostaglandin (PG)F2α and 11-dehydro-thromboxane (TX)B2 (markers of in vivo lipid peroxidation and platelet activation, respectively) was performed in 100 carriers and 100 non-carriers of the polymorphism. A methionine-loading test and folic acid supplementation were performed to investigate the causal relationship of the observed associations. Urinary 8-iso-PGF2α and 11-dehydro-TXB2 were higher in carriers with hyperhomocysteinaemia than in those without hyperhomocysteinaemia (p<0.0001). Hyperhomocysteinaemic carriers had lower folate levels (p=0.0006), higher urinary 8-iso-PGF2α (p<0.0001) and 11-dehydro-TXB2 (p<0.0001) than hyperhomocysteinaemic non-carriers. On multiple regression analysis, high tHcy (p<0.0001), low folate (p<0.04) and MTHFR 677 C→T polymorphism (p<0.001) independently predicted high rates of 8-iso-PGF2α excretion. Methionine loading increased plasma tHcy (p=0.002), and both urinary prostanoid metabolites (p=0.002). Folic acid supplementation was associated with decreased urinary 8-iso-PGF2α and 11-dehydro-TXB2 excretion (p<0.0003) in the hyperhomocysteinaemic group, but not in the control group, with substantial inter-individual variability related to baseline tHcy level and the extent of its reduction. In conclusion, hyperhomocysteinaemia due to the MTHFR 677 C→T polymorphism is associated with enhanced in vivo lipid peroxidation and platelet activation that are reversible, at least in part, following folic acid supplementation. An integrated biomarker approach may help identifying appropriate candidates for effective folate supplementation.
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Di Minno, Alessandro, Achille Aveta, Monica Gelzo, Lorella Tripodi, Savio Domenico Pandolfo, Felice Crocetto, Ciro Imbimbo y Giuseppe Castaldo. "8-Hydroxy-2-Deoxyguanosine and 8-Iso-Prostaglandin F2α: Putative Biomarkers to assess Oxidative Stress Damage Following Robot-Assisted Radical Prostatectomy (RARP)". Journal of Clinical Medicine 11, n.º 20 (17 de octubre de 2022): 6102. http://dx.doi.org/10.3390/jcm11206102.
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Objective: Prostate cancer (PCa) is the most common type of cancer. Biomarkers help researchers to understand the mechanisms of disease and refine diagnostic panels. We measured urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-IsoF2α) to assess oxidative stress damage in PCa patients undergoing robot-assisted radical prostatectomy (RARP). Methods: Forty PCa patients were enrolled in the study. Urine was collected before (T0) and 3 months after the RARP procedure (T1). 8-OHdG and 8-IsoF2α were measured through liquid chromatography-tandem mass spectrometry. Sex- and age-matched healthy subjects served as controls (CTRL). Results: At T0, patients exhibited significantly higher levels of 8-OHdG than CTRL (p = 0.026). At T1, 23/40 patients who completed the 3-month follow-up showed levels of 8-OHdG that were significantly lower than at T0 (p = 0.042), and comparable to those of the CTRL subjects (p = 0.683). At T0, 8-Iso-PGF2α levels were significantly higher in PCa patients than in CTRL subjects (p = 0.0002). At T1, 8-Iso-PGF2α levels were significantly lower than at T0 (p < 0.001) and were comparable to those of CTRL patients (p = 0.087). Conclusions: A liquid chromatography-tandem mass spectrometry method reveals enhanced OHdG and 8-Iso-PGF2α in the urine of PCa patients. RARP normalizes such indices of oxidative stress. Large-sized sample studies and long-term follow-ups are now needed to validate these urinary biomarkers for use in the early prevention and successful treatment of PCa.
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BASU, S., U. RISÉRUS, A. TURPEINEN y B. VESSBY. "Conjugated linoleic acid induces lipid peroxidation in men with abdominal obesity". Clinical Science 99, n.º 6 (7 de noviembre de 2000): 511–16. http://dx.doi.org/10.1042/cs0990511.
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Conjugated linoleic acid (CLA) has been shown in experimental studies to have chemoprotective properties, and may decrease the deposition of body fat. CLA is prone to oxidation, and it has been suggested that increased lipid oxidation may contribute to the anti-tumorigenic effects of this agent. The present study investigates the urinary levels of 8-iso-prostaglandin F2α (8-iso-PGF2α), a major isoprostane, and of 15-oxo-dihydro-PGF2α, a major metabolite of PGF2α, as indicators of non-enzymic and enzymic arachidonic acid oxidation respectively after dietary supplementation with CLA in middle-aged men (mean age 53 years) with abdominal obesity for 1 month in a randomized controlled trial. Significant increases in the levels of both 8-iso-PGF2α and 15-oxo-dihydro-PGF2α in urine (P < 0.0001 and P = 0.0013 respectively) were observed after 1 month of daily CLA intake (4.2 g/day) as compared with the control group. The lipid peroxidation parameters had returned to their basal levels at 2 weeks after the cessation of CLA intake, and remained at the same levels for a further 2 weeks until the end of the study. CLA had no effect on serum α-tocopherol and γ-tocopherol levels, or on the urinary levels of 2,3-dinor-thromboxane B2. Thus CLA may induce both non-enzymic and enzymic lipid peroxidation in vivo in middle-aged men with abdominal obesity, without any side effects. The consequences of the increased lipid peroxidation after CLA supplementation are unknown.
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Tsai, Yu-Lien, Chih-Wei Liu, Chien-Fu Hsu, Chia-Chang Huang, Ming-Wei Lin, Shiang-Fen Huang, Tzu-Hao Li et al. "Obeticholic acid ameliorates hepatorenal syndrome in ascitic cirrhotic rats by down-regulating the renal 8-iso-PGF2α-activated COX-TXA2 pathway". Clinical Science 134, n.º 15 (agosto de 2020): 2055–73. http://dx.doi.org/10.1042/cs20200452.
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Abstract Backgrounds/Aims: The present study explores the potential of chronic treatment with the Foresaid X receptor (FXR) agonist obeticholic acid (OCA), which inhibits oxidative stress-related pathogenesis, in ascitic cirrhotic rats with hepatorenal syndrome (HRS) developed 6 weeks after bile duct ligation (BDL). Methods: Systemic, splanchnic, and renal hemodynamics and pathogenic cascades were measured in ascitic BDL and sham rats receiving 2-weeks of either vehicle or OCA treatments (sham-OCA and BDL-OCA groups), and NRK-52E cells, rat kidney tubular epithelial cells. Results: Chronic OCA treatment significantly normalized portal hypertension, glomerular filtration rate, urine output, renal blood flow; decreased ascites, renal vascular resistance, serum creatinine, and the release of renal tubular damage markers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury moleculae-1 (uKim-1) in BDL-OCA rats. In the BDL group, inhibition of the renal oxidative stress (8-iso-PGF2α)-activated cyclooxygenase-thromboxane A2 [COX-TXA2] pathway, apoptosis, and tubular injury accompanied by a decrease in hyper-responsiveness to the vasoconstrictor 8-iso-PGF2α in perfused kidneys. In vitro experiments revealed that 8-iso-PGF2α induced oxidative stress, release of reactive oxygen species, and cell apoptosis, which were reversed by concomitant incubation with the FXR agonist. Conclusions: Through the inhibition of renal 8-iso-PGF2α production and the down-regulation of the COX-TXA2 pathway, our study suggests that chronic OCA treatment can ameliorate the HRS in ascitic cirrhotic rats. Thus, OCA is an agent with antioxidative stress, antivasoconstrictive, antiapoptotic properties which benefit ascitic, cirrhotic rats with systemic, hepatic, and renal abnormalities.
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Wang, Qingqing, Sha Tian, Dahai Xiao, Ruotong Zhao, Xiaoxuan Zhang, Zhijie Dou, Chengbo Li y Zheng Ma. "Correlation of serum RBP4 level with oxidative stress and unstable carotid plaque in patients with cerebral infarction". Translational Neuroscience 13, n.º 1 (1 de enero de 2022): 354–60. http://dx.doi.org/10.1515/tnsci-2022-0252.
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Abstract Objectives This study aimed to investigate the changes in serum levels of retinol-binding protein 4 (RBP4) with cerebral infarction, relationship of RBP4 with oxidative stress and carotid atherosclerosis, and its possible role in cerebral infarction. Materials and methods According to the results of cervical vascular ultrasound, the experimental group was divided into three groups: intima thickening group (n = 31), stable plaque group (n = 51), and unstable plaque group (n = 54). Forty healthy subjects were selected as the control group. Their serum levels of RBP4, 8-iso-prostaglandin-F2alpha (8-iso-PGF2α), and catalase (CAT) were measured. Carotid vascular ultrasound was used to measure the plaque area and intima-media thickness (IMT). Results The serum RBP4 and 8-iso-PGF2α levels, IMT and plaque area in the control, intimal thickening, stable plaque, and unstable plaque groups increased, while the serum level of CAT decreased (P < 0.001). The serum levels of RBP4 positively correlated with 8-iso-PGF2α, IMT, and plaque area and negatively correlated with CAT level. The area under the receiver operating characteristic curve was 0.778 in predicting unstable plaques. Conclusions The serum levels of RBP4 were significantly elevated in elderly patients with cerebral infarction and correlated with oxidative stress injury and the degree of atherosclerosis. Serum RBP4 has diagnostic value for unstable plaques in carotid arteries.
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Desideri, Giovambattista, Giuseppe Croce, Marzia Tucci, Gabriella Passacquale, Simona Broccoletti, Letizia Valeri, Anna Santucci y Claudio Ferri. "Effects of Bezafibrate and Simvastatin on Endothelial Activation and Lipid Peroxidation in Hypercholesterolemia: Evidence of Different Vascular Protection by Different Lipid-Lowering Treatments". Journal of Clinical Endocrinology & Metabolism 88, n.º 11 (1 de noviembre de 2003): 5341–47. http://dx.doi.org/10.1210/jc.2003-030724.
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Abstract Hypercholesterolemia is combined with enhanced lipid peroxidation, which can promote atherogenesis by inducing endothelial adhesion molecule expression. Statins may protect vascular endothelium in hypercholesterolemia by reducing enhanced plasma levels of low-density lipoprotein and decreasing oxidative stress. Herein, we describe increased circulating levels of soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin and total 8-iso-prostaglandin F2α (8-iso-PGF2α) concentrations, as indexes of endothelial activation and lipid peroxidation, respectively, in 67 hypercholesterolemic patients compared with 32 normocholesterolemic subjects. Significant cholesterol reductions were achieved in hypercholesterolemic patients after 6 months under either simvastatin (40 mg/d) or bezafibrate (800 mg/d) treatment, given according to a randomized double-blind trial. Simvastatin but not bezafibrate simultaneously reduced soluble adhesin and total 8-iso-PGF2α concentrations also. Vitamin E supplementation (400 IU/d) further reduced indexes of endothelial activation and lipid peroxidation in simvastatin-treated patients and significantly reduced the above indexes in bezafibrate-treated patients. Changes in circulating soluble adhesion molecule levels were directly correlated with changes in total 8-iso-PGF2α concentrations in simvastatin-treated patients also receiving vitamin E supplementation. All together, our data demonstrated that hypercholesterolemia was combined with endothelial activation and lipid peroxidation, which were efficaciously counteracted by simvastatin but not bezafibrate treatment. Thus, a different vascular protection can be achieved by different lipid-lowering treatments.
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Zhou, Yan, Lianjie Zhang, Jingjing Guan y Xin Yin. "Improvement of lung ischemia–reperfusion injury by inhibition of microRNA-155 via reductions in neuroinflammation and oxidative stress of vagal afferent nerve". Pulmonary Circulation 10, n.º 2 (abril de 2020): 204589402092212. http://dx.doi.org/10.1177/2045894020922125.
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Lung ischemia–reperfusion injury (LIRI) is a common clinical concern. As the injury occurs, the pulmonary afferent nerves play a key role in regulating respiratory functions under pathophysiological conditions. The present study was to examine the effects of inhibiting microRNA-155 on the levels of proinflammatory cytokines and products of oxidative stress in the pulmonary vagal afferent nerves and the commissural nucleus of the solitary tract (cNTS) after LIRI. A rat model of LIRI was used. ELISA method was employed to examine proinflammatory cytokines, namely, IL-1β, IL-6 and TNF-α; and key biomarkers of oxidative stress, 8-isoprostaglandin F2α (8-iso PGF2α) and 8-hydroxy-2′-deoxyguanosine (8-OHdG). In results, in the process of LIRI, the levels of microRNA-155 were amplified in the vagal afferent nerves and cNTS, and this was accompanied with increases of IL-1β, IL-6 and TNF-α; and 8-iso PGF2α and 8-OHdG. Application of microRNA-155 inhibitor, but not its scramble, attenuated the elevation of proinflammatory cytokines and amplification of 8-iso PGF2α and 8-OHdG in those nerve tissues. In conclusion, we observed the abnormalities in the pulmonary afferent pathways at the levels of the peripheral nerves and brainstem, which is likely to affect respiratory functions as LIRI occurs. Our data suggest that blocking microRNA-155 signal pathways plays a beneficial role in regulating LIRI via inhibiting responses of neuroinflammation and oxidative stress signal pathways to LIRI.
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Yu, Rui, Guiqing Zhao, John W. Christman, Lei Xiao y Richard B. van Breemen. "Method Development and Validation for Ultra-High Pressure Liquid Chromatography/Tandem Mass Spectrometry Determination of Multiple Prostanoids in Biological Samples". Journal of AOAC INTERNATIONAL 96, n.º 1 (1 de enero de 2013): 67–76. http://dx.doi.org/10.5740/jaoacint.12-280.
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Abstract Following oxygenation of arachidonic acid by cyclooxygenase to form prostaglandin H2 (PGH2), a variety of prostanoids can be generated with diverse physiologic effects on pain, inflammation, allergy, cardiovascular system, cancer, etc. To facilitate the quantitative analysis of prostanoids in human serum of cell culture, an ultra-high pressure LC (UHPLC)/MS/MS method was developed and validated for the measurement of six eicosanoids belonging to the cyclooxygenase pathway: PGE2, PGD2, 8-iso-PGF2α, PGF2α, 6-keto-PGF1α, and thromboxane B2 (TXB2 ). Selectivity, matrix effects, calibration model, precision, and accuracy (intraday and interday), lower limit of quantitation (LLOQ), recovery, stability, and sample dilution were evaluated. Fast UHPLC separation was carried out in only 0.5 min with isocratic elution, and each prostanoid was measured using negative electrospray ionization MS with collision-induced dissociation and selected reaction monitoring. UHPLC/MS/MS provided high throughput with peak widths of approximately 3 s and an LLOQ of 0.020 ng/mL for PGE2, 0.027 ng/mL for PGD2, 0.152 ng/mL for 8-iso-PGF2α, 0.179 ng/mL for PGF2α and 6-keto-PGF1α, and 0.013 ng/mL for TXB2.
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Belik, J., R. P. Jankov, J. Pan, M. Yi, I. Chaudhry y A. K. Tanswell. "Chronic O2 exposure in the newborn rat results in decreased pulmonary arterial nitric oxide release and altered smooth muscle response to isoprostane". Journal of Applied Physiology 96, n.º 2 (febrero de 2004): 725–30. http://dx.doi.org/10.1152/japplphysiol.00825.2003.
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Chronic oxygen exposure in the newborn rat results in lung isoprostane formation, which may contribute to the pulmonary hypertension evident in this animal model. The purpose of this study was to investigate the pulmonary arterial smooth muscle responses to 8-iso-prostaglandin F2α (8-iso-PGF2a) in newborn rats exposed to 60% O2 for 14 days. Because, in the adult rat, 8-iso-PGF2α may have a relaxant effect, mediated by nitric oxide (NO), we also sought to evaluate the pulmonary arterial NO synthase (NOS) protein content and NO release in the newborn exposed to chronic hyperoxia. Compared with air-exposed control animals, 8-iso-PGF2a induced a significantly greater force ( P < 0.01) and reduced ( P < 0.01) relaxation of precontracted pulmonary arteries in the 60% O2-treated animals. These changes were reproduced in control pulmonary arteries by NOS blockade by using NG-nitro-l-arginine methyl ester. Pulmonary arterial endothelial NOS was unaltered, but the inducible NOS protein content was significantly decreased ( P < 0.01) in the experimental group. Pulmonary ( P < 0.05) and aortic ( P < 0.01) tissue ex vivo NO accumulation was significantly reduced in the 60% O2-treated animals. We speculate that impaired pulmonary vascular tissue NO metabolism after chronic O2 exposure potentiates 8-iso-PGF2α-induced vasoconstriction in the newborn rat, thus contributing to pulmonary hypertension.
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Cheng, Ling, Weibiao Cao, Jose Behar, Piero Biancani y Karen M. Harnett. "Inflammation induced changes in arachidonic acid metabolism in cat LES circular muscle". American Journal of Physiology-Gastrointestinal and Liver Physiology 288, n.º 4 (abril de 2005): G787—G797. http://dx.doi.org/10.1152/ajpgi.00327.2004.
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Myogenic lower esophageal sphincter (LES) tone is maintained by arachidonic acid metabolites, such as PGF2α and thromboxane A2/B2. Experimental esophagitis in cat reduces LES in vivo pressure and in vitro tone. Because IL-1β may mediate esophagitis-associated reduction in ACh release in esophagus, we examined whether IL-1β may also play a role in esophagitis-induced reduction of LES tone. A cat model of experimental esophagitis was obtained by repeated esophageal perfusion with HCl (Biancani P, Barwick K, Selling J, and McCallum R. Gastreonterology 87: 8–16, 1984 and Sohn UD, Harnett KM, Cao W, Rich H, Kim N, Behar J, and Biancani P. J Pharmacol Exp Ther 283: 1293–1304, 1997.). LES circular muscle strips were examined in muscle chambers as previously described (Biancani P, Billett G, Hillemeier C, Nissenshon M, Rhim BY, Sweczack S, and Behar J. Gastroenterology 103: 1199–1206, 1992). Levels of inflammatory mediators were measured. IL-1β levels were higher in esophagitis than in normal LES. IL-1β reduced normal LES tone, and the reduction was reversed by catalase, suggesting a role of H2O2. This was confirmed by IL-1β-induced production of H2O2 in normal LES and elevated H2O2 levels in esophagitis. H2O2 by itself is sufficient to explain the changes that occur in the muscle, reducing its ability to contract. H2O2 increased PGE2 in normal LES, and PGE2 levels were elevated in esophagitis LES, whereas PGF2α levels were unchanged. H2O2 also increased levels of 8-isoprostanes, stable prostaglandin-like compounds formed by free radical-induced peroxidation of arachidonic acid, and 8-isoprostane levels were elevated in esophagitis. The PGF2α analog 8-iso-PGF2α caused little contraction of LES strips but reduced PGF2α binding and contraction of normal LES. In esophagitis, PGF2α binding and contraction were reduced in LES, suggesting that isoprostanes may contribute to reduction in tone in esophagitis. The data suggest that, in esophagitis, IL-1β causes production of H2O2. H2O2 increases PGE2, which relaxes the LES, and 8-iso-F2α, which blocks PGF2α-mediated contraction.
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AVOUAC, JEROME, DIDIER BORDERIE, OVANESSE GARABED EKINDJIAN, ANDRE KAHAN y YANNICK ALLANORE. "High DNA Oxidative Damage in Systemic Sclerosis". Journal of Rheumatology 37, n.º 12 (15 de septiembre de 2010): 2540–47. http://dx.doi.org/10.3899/jrheum.100398.
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Objective.Several lines of evidence suggest that the generation of reactive oxygen species (ROS) is of major importance in the pathogenesis of SSc. Protein and lipid damage have previously been demonstrated, but scarce data are available on oxidative damage to DNA. In patients with SSc, we evaluated levels of 8-hydroxy-2’-deoxyguanosine (8-oxodG), the main validated biomarker of endogenous oxidative damage to DNA, compared to levels of F2-isoprostane, a product of free radical-mediated peroxidation of arachidonic acid.Methods.Urinary levels of 8-oxodG and 8-isoprostaglandin-F2α (8-iso-PGF2α) were determined by competitive ELISA method in consecutive SSc patients and controls matched for age and sex.Results.We included 80 unrelated SSc patients (72 women, mean age 56 ± 11 yrs) and 39 controls (33 women, mean age 64 ± 8 yrs). Urinary levels of 8-oxodG/creat and 8-iso-PGF2α/creat in SSc patients were found to be higher than in controls (6.5 ng/mg vs 3.7 ng/mg, p = 0.0001; and 11.4 ng/mg vs 4.2 ng/mg, p < 0.0001). In multivariate analysis, 8-oxodG levels were associated with the presence of pulmonary fibrosis on computerized tomography scan, decreased forced vital capacity, and decreased DLCO/alveolar volume. In patients with the diffuse cutaneous subset, a modified Rodnan skin score > 14 was independently associated with 8-oxodG levels. In SSc, 8-oxodG and 8-iso-PGF2α values were correlated (r = 0.32; p = 0.005).Conclusion.Our study confirmed marked oxidative stress in SSc. We also found increased values of 8-oxodG in SSc patients and a relevant association with a fibrotic phenotype. The predictive value of this marker and its potential influence on fibrotic disturbances remain to be determined.
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Guerci, Marco, Paola Simeone, Sandro Ardizzone, Alessandro Massari, Paolo Giuffrida, Romina Tripaldi, Alessandro Malara et al. "Oxidative stress and thromboxane-dependent platelet activation in inflammatory bowel disease: effects of anti-TNF-α treatment". Thrombosis and Haemostasis 116, n.º 09 (2016): 486–95. http://dx.doi.org/10.1160/th16-02-0167.
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SummaryPatients with inflammatory bowel disease (IBD) are at higher risk of venous thromboembolism and coronary artery disease despite having a lower burden of traditional risk factors. Platelets from IBD patients release more soluble CD40 ligand (CD40L), and this has been implicated in IBD platelet hyper-activation. We here measured the urinary F2-isoprostane 8-iso-prostaglandin (PG)2α (8-iso-PGF2α), urinary 11–dehydro–thromboxane (TX) B2 (11-dehydro–TXB2) and plasma CD40L in IBD patients, and explored the in vitro action of anti-tumour necrosis factor (TNF)–α antibody infliximab on IBD differentiating megakaryocytes. Urinary and blood samples were collected from 124 IBD patients and 37 healthy subjects. Thirteen IBD patients were also evaluated before and after 6–week infliximab treatment. The in vitro effect of infliximab on patient-derived megakaryocytes was evaluated by immunoflorescence microscopy and by flow cytometry. IBD patients had significantly (p<0.0001) higher urinary 8–iso–PGF2α and 11–dehydro–TXB2 as well as plasma CD40L levels than controls, with active IBD patients displaying higher urinary and plasma values when compared to inactive patients in remission. A 6-week treatment with infliximab was associated with a significant reduction of the urinary excretion of 8–iso–PGF2α and 11–dehydro–TXB2 (p=0.008) and plasma CD40L (p=0.001). Infliximab induced significantly rescued pro-platelet formation by megakaryocytes derived from IBD patients but not from healthy controls. Our findings provide evidence for enhanced in vivo TX–dependent platelet activation and lipid peroxidation in IBD patients. Anti-TNF–α therapy with infliximab down-regulates in vivo isoprostane generation and TX biosynthesis in responder IBD patients. Further studies are needed to clarify the implication of infliximab induced-proplatelet formation from IBD megakaryocytes.Supplementary Material to this article is available online at www.thrombosis-online.com.
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Noble, S., D. Neville y R. Houghton. "Determination of 8-iso-prostaglandin F2α (8-iso-PGF2α) in human urine by ultra-performance liquid chromatography–tandem mass spectrometry". Journal of Chromatography B 947-948 (febrero de 2014): 173–78. http://dx.doi.org/10.1016/j.jchromb.2013.12.028.
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Lados-Krupa, Anna, Malgorzata Konieczynska, Artur Chmiel y Anetta Undas. "Increased Oxidation as an Additional Mechanism Underlying Reduced Clot Permeability and Impaired Fibrinolysis in Type 2 Diabetes". Journal of Diabetes Research 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/456189.
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Aims. We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes.Methods. We assessed plasma fibrin clot permeation (Ks, a measure of the pore size in fibrin networks) and clot lysis time induced by recombinant tissue plasminogen activator (CLT) in 163 consecutive type 2 diabetic patients (92 men and 71 women) aged 65 ± 8.8 years with a mean glycated hemoglobin (HbA1c) of 6.8%. We also measured oxidative stress markers, including nitrotyrosine, the soluble form of receptor for advanced glycation end products (sRAGE), 8-iso-prostaglandin F2α(8-iso-PGF2α), oxidized low-density lipoprotein (oxLDL), and advanced glycation end products (AGE).Results. There were inverse correlations betweenKsand nitrotyrosine, sRAGE, 8-iso-PGF2α, and oxLDL. CLT showed a positive correlation with oxLDL and nitrotyrosine but not with other oxidation markers. All these associations remained significant forKsafter adjustment for fibrinogen, disease duration, and HbA1c (allP<0.05), while oxLDL was the only independent predictor of CLT.Conclusions. Our study shows that enhanced oxidative stress adversely affects plasma fibrin clot properties in type 2 diabetic patients, regardless of disease duration and glycemia control.
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Welch, William J. "Effects of isoprostane on tubuloglomerular feedback: roles of TP receptors, NOS, and salt intake". American Journal of Physiology-Renal Physiology 288, n.º 4 (abril de 2005): F757—F762. http://dx.doi.org/10.1152/ajprenal.00269.2004.
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A thromboxane prostanoid receptor (TP-R) agonist U-46,619 enhances tubuloglomerular feedback (TGF). Glomerular expression of TP-R and enhancement of TGF by U-46,619 increase with salt intake. We investigated the hypothesis that 8-isoprostaglandin F2α (8-Iso) activates TGF via TP-R. The maximal TGF response in rats was assessed from the fall in proximal stop flow pressure (PSF; an index of glomerular capillary pressure) during loop of Henle (LH) microperfusion of artificial tubular fluid (ATF) at 40 nl/min. Microperfusion of 8-Iso (10−4 M) into the efferent arteriole (EA) enhanced TGF responses by 20 ± 3% ( P < 0.01). TGF response to 8-Iso was independent of dietary salt [ΔTGF%, low salt (LS): 21 ± 5%; normal salt (NS): 17 ± 4%; high salt (HS): 29 ± 8%, not significant (ns)], unlike the salt-dependent effect of U-46,619 (ΔTGF%, LS: 41 ± 5%; NS: 52 ± 4%; HS: 112 ± 21%). Ifetroban, the TP-R antagonist, abolished TGF responses to 8-Iso and U-46,619 at all levels of salt intake. During luminal perfusion of N-monomethyl-l-arginine (l-NMA), the effect of 8-Iso on TGF was enhanced in NS and HS but not in LS (LS: 22 ± 6 vs. LS + l-NMA: 28 ± 6%, ns; NS: 18 ± 4 vs. NS + l-NMA: 40 ± 4, P < 0.01; HS: 27 ± 3 vs. HS + l-NMA: 65 ± 6, P < 0.01). However, U-46,619 did not further increase TGF after l-NMA in all salt groups (LS: 43 ± 7 vs. LS + l-NMA: 51 ± 6, ns; NS: 52 ± 7 vs. NS + l-NMA: 48 ± 8, ns; HS: 114 ± 21 vs. HS + l-NMA: 74 ± 22, ns). In conclusion, activation of TP receptors by U-46,619 and 8-Iso-PGF2α enhances TGF. In addition, the effect of U-46,619 was salt dependent, whereas the effect of 8-Iso-PGF2α was salt independent. However, stimulation of NO by 8-isoprostanes masks its salt-sensitive effect on TGF.
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Ashrap, Pahriya, Deborah J. Watkins, Ginger L. Milne, Kelly K. Ferguson, Rita Loch-Caruso, Jennifer Fernandez, Zaira Rosario et al. "Maternal Urinary Metal and Metalloid Concentrations in Association with Oxidative Stress Biomarkers". Antioxidants 10, n.º 1 (15 de enero de 2021): 114. http://dx.doi.org/10.3390/antiox10010114.
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Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9% for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.
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Cuccurullo, Chiara, Dario Di Michele, Giuseppe Laurora, Giuseppe Sgrò, Paolo Di Ruscio, Emilio Simeone, Pierangelo Di Iorio et al. "Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: Beneficial effects of iloprost". Thrombosis and Haemostasis 105, n.º 02 (2011): 321–28. http://dx.doi.org/10.1160/th10-07-0499.
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SummaryPlatelets critically contribute to atherothrombosis and worsening ischaemia in patients with peripheral arterial disease (PAD), eventually leading to critical limb ischaemia (CLI). Furthermore, persistent platelet activation despite antiplatelet therapy has been reported in this setting. The prostacyclin analogue iloprost is currently recommended in CLI patients for its effects in relieving symptoms by promoting local perfusion. In this study, we investigated the effects of iloprost infusion on urinary 11-dehydro-TXB2 and 8-iso-PGF2α excretion rate, as in vivoindexes of thromboxane-dependent platelet activation and lipid peroxidation, respectively, and on platelet-derived proinflammatory sCD40L and nitric oxide bioavailability in 44 patients with CLI while on chronic treatment with low-dose aspirin. Daily iloprost infusion for one-week significantly decreased urinary 11-dehydro-TXB2 [499 (277 – 807) vs. 380 (189 – 560) pg/mg creatinine, p < 0.0001] and 8-iso-PGF2α [533 (316 – 842) vs. 334 (196 – 540) pg/mg creatinine, p < 0.0001] as well as plasma sCD40L [1540 (1005 – 3015) vs. 948 (845 – 2030) pg/ml, p < 0.0001]. Furthermore, a significant increase in plasma nitrate plus nitrite levels has been observed [26.8 (18.8 – 35.9) vs. 43.7 (33.0 – 75.5) μM, p < 0.0001]. A significant direct correlation was also found between urinary 8-iso-PGF2α and 11-dehydro-TXB2 before and after iloprost treatment (Rho = 0.695, p < 0.0001). In conclusion, we report that a short-term course of iloprost is able to significantly reduce residual thromboxane biosynthesis, oxidative stress, endothelial dysfunction and platelet-derived inflammation in low-dose aspirin treated patients with CLI.
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van ‘t Erve, Thomas J., Fred B. Lih, Maria B. Kadiiska, Leesa J. Deterding, Thomas E. Eling y Ronald P. Mason. "Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF2α/PGF2α ratio distinguishes chemical from enzymatic lipid peroxidation". Free Radical Biology and Medicine 83 (junio de 2015): 245–51. http://dx.doi.org/10.1016/j.freeradbiomed.2015.03.004.
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Kuriyama, Shinichi, Satoru Ebihara, Atsushi Hozawa, Kaori Ohmori, Kayoko Kurashima, Naoki Nakaya, Toshifumi Matsui et al. "Dietary Intakes and Plasma 8-Iso-Prostaglandin F2α Concentrations in Community-Dwelling Elderly Japanese: The Tsurugaya Project". International Journal for Vitamin and Nutrition Research 76, n.º 2 (1 de marzo de 2006): 87–94. http://dx.doi.org/10.1024/0300-9831.76.2.87.
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We examined the association between dietary intakes and oxidative stress status in elderly Japanese. We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment conducted in 2002. The subjects included 961 Japanese subjects aged 70 years or older who were non-daily antioxidant supplements users. We measured plasma total 8-iso-prostaglandin (PG)F2α concentrations, a measurable lipid peroxidation biomarker, using a specific enzyme immunoassay kit. Dietary intakes were assessed through a food frequency questionnaire. Subjects were divided into three groups according to their dietary intake frequencies. Logistic regression was applied to calculate the odds ratios (ORs) for being in the highest tertile of plasma 8-iso-PGF2α concentration. Frequent intake of orange or other citrus fruits, or persimmon, strawberry, or kiwi fruit was associated with lower plasma 8-iso-PGF2α concentrations, respectively. After adjustment for potential confounders, the ORs and 95% confidence intervals (CIs) for orange or other citrus fruits were 1.00 (reference), 0.66 (0.47, 0.92), and 0.58 (0.39, 0.87) (p for trend, 0.009). Intake of persimmon, strawberry, or kiwi fruit showed similar results. These associations were partly explained by vitamin C intake. Other dietary intakes had no association. Intake of fruits may have a beneficial effect against oxidative stress in elderly Japanese.
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Roberts, Christian K., Brian H. Chen, Sandeep Pruthi y Martin L. Lee. "Effects of varying doses of testosterone on atherogenic markers in healthy younger and older men". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 306, n.º 2 (15 de enero de 2014): R118—R123. http://dx.doi.org/10.1152/ajpregu.00372.2013.
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Whether exogenous testosterone is proatherogenic remains controversial. We assessed the effects of graded doses of testosterone on serum markers of oxidative stress, chemotaxis, adhesion, and inflammation in healthy younger and older men. In a double-blind, randomized trial, 121 eugonadal men ( n = 61, 18–35 years of age and n = 60, 60–75 years of age) were randomized to one of five groups to receive weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk, respectively, along with a long-acting gonadotropin-releasing hormone (GnRH) agonist. Energy and protein intakes were standardized and no resistance training was allowed. We measured plasma levels of the atherogenic biomarkers monocyte chemotactic protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1), 8-isoprostane-PGF2α (8-iso-PGF2α), and high-sensitivity C-reactive protein (hs-CRP) before and after the intervention. Administration of increasing doses of testosterone led to reduction in total 8-iso-PGF2α in the younger (p-trendYounger = 0.01), but not older (p-trendOlder = 0.79) men. No significant linear associations were observed between testosterone dose and MCP-1, sICAM-1, or hs-CRP (all p-trend >0.20). In apparently healthy men, over a wide dose range, testosterone did not adversely affect atherogenic biomarkers. Long-term studies with larger sample sizes are warranted to determine whether testosterone supplementation affects atherosclerosis progression and cardiovascular risk.
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Zhu, Tao, Shanqun Li, Jiajia Wang, Chunfang Liu, Lei Gao, Yuzhen Zeng, Ruolin Mao, Bo Cui, Hong Ji y Zhihong Chen. "Induced sputum metabolomic profiles and oxidative stress are associated with chronic obstructive pulmonary disease (COPD) severity: potential use for predictive, preventive, and personalized medicine". EPMA Journal 11, n.º 4 (4 de noviembre de 2020): 645–59. http://dx.doi.org/10.1007/s13167-020-00227-w.
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AbstractChronic obstructive pulmonary disease (COPD) is a highly heterogeneous disease, and metabolomics plays a hub role in predictive, preventive, and personalized medicine (PPPM) related to COPD. This study thus aimed to reveal the role of induced sputum metabolomics in predicting COPD severity. In this pilot study, a total of 20 COPD patients were included. The induced sputum metabolites were assayed using a liquid chromatography-mass spectrometry (LC-MS/MS) system. Five oxidative stress products (myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione (GSH), neutrophil elastase (NE), and 8-iso-PGF2α) in induced sputum were measured by ELISA, and the metabolomic profiles were distinguished by principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA). The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis, and a significant difference in induced sputum metabolomics was observed between moderate and severe COPD. The KEGG analysis revealed that the glycerophospholipid metabolism pathway was downregulated in severe COPD. Due to the critical role of glycerophospholipid metabolism in oxidative stress, significant negative correlations were discovered between glycerophospholipid metabolites and three oxidative stress products (SOD, MPO, and 8-iso-PGF2α). The diagnostic values of SOD, MPO, and 8-iso-PGF2α in induced sputum were found to exhibit high sensitivities and specificities in the prediction of COPD severity. Collectively, this study provides the first identification of the association between induced sputum metabolomic profiles and COPD severity, indicating the potential value of metabolomics in PPPM for COPD management. The study also reveals the correlation between glycerophospholipid metabolites and oxidative stress products and their value for predicting COPD severity.
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Belli, R., P. Amerio, L. Brunetti, G. Orlando, P. Toto, G. Proietto, M. Vacca y A. Tulli. "Elevated 8-Isoprostane Levels in Basal Cell Carcinoma and in Uva Irradiated Skin". International Journal of Immunopathology and Pharmacology 18, n.º 3 (julio de 2005): 497–502. http://dx.doi.org/10.1177/039463200501800309.
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Isoprostanes are prostaglandin isomers produced from the peroxidation of polyunsaturated fatty acids from the cellular membrane. They have been used as a specific index of cellular lipoperoxidation and as an indirect measure of oxidative stress. However, these molecules also present several biological activities. An oxidative environment measured as the presence of other indirect measurements of reactive oxygen species lipoperoxidation has recently been described in basal cell carcinoma, the most frequent type of non-melanoma skin cancer. This study aims to measure the levels of 8-isoprostaglandin F2α, an isoprostane widely studied in other models as a by-product of ROS-induced lipid peroxidation, in basal cell carcinoma and in UVA irradiated healthy skin. We found that 8-iso-PGF2α is present in higher levels in BCC specimens compared to healthy non sun-exposed skin, confirming previous studies on the production of lipoperoxidation in this tumor. Moreover, we demonstrated that topical pre-treatment with a compound containing vitamin E is capable of reducing 8-iso-PGF2α formation in UV irradiated skin suggesting a role for isoprostanes in UV induced inflammation and eventually carcinogenesis and confirming the function of vitamin E as an antioxidant in this model.
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Lepara, Orhan, Asija Zaciragic, Almir Fajkic, Alma Dzubur Kulenovic, Amela Dervisevic, Amina Valjevac, Emina Kiseljakovic y Saida Ibragic. "PERIPHERAL 8-ISO-PGF2Α AS A BIOMARKER IN BOSNIAN PATIENTS WITH ALZHEIMER’S DISEASE AND VASCULAR DEMENTIA". Psychiatria Danubina 32, n.º 3-4 (24 de diciembre de 2020): 389–94. http://dx.doi.org/10.24869/psyd.2020.389.
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Santilli, Francesca, Rossella Liani, Patrizia Di Fulvio, Gloria Formoso, Paola Simeone, Romina Tripaldi, Thor Ueland, Pål Aukrust y Giovanni Davì. "Increased circulating resistin is associated with insulin resistance, oxidative stress and platelet activation in type 2 diabetes mellitus". Thrombosis and Haemostasis 116, n.º 12 (noviembre de 2016): 1089–99. http://dx.doi.org/10.1160/th16-06-0471.
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SummaryResistin is an adipokine that promotes inflammation and insulin resistance by targeting several cells including platelets. We hypothesised that in type 2 diabetes (T2DM), resistin may foster in vivo oxidative stress, thromboxane-dependent platelet activation and platelet-derived inflammatory proteins release, key determinants of atherothrombosis. A cross-sectional comparison of circulating resistin, sCD40L, as a marker of platelet-mediated inflammation, asymmetric dimethylarginine (ADMA), endothelial dysfunction marker, Dickkopf (DKK)-1, reflecting the inflammatory interaction between platelets and endothelial cells, and urinary 8-iso-PGF2α and 11-dehydro-TxB2, reflecting in vivo lipid peroxidation and platelet activation, respectively, was performed between 79 T2DM patients and 30 healthy subjects. Furthermore, we investigated the effects of the α-glucosidase inhibitor acarbose and the PPARγ agonist rosiglitazone, targeting hyperglycaemia or insulin resistance, versus placebo, in 28 and 18 T2DM subjects, respectively. Age- and gender-adjusted serum resistin levels were significantly higher in patients than in controls. HOMA (β=0.266, p=0.017) and 11-dehydro-TXB2 (β=0.354, p=0.002) independently predicted resistin levels. A 20-week treatment with acarbose was associated with significant reductions (p=0.001) in serum resistin, DKK-1, urinary 11-dehydro-TXB2 and 8-iso-PGF2α with direct correlations between the change in serum resistin and in other variables. A 24-week rosiglitazone treatment on top of metformin was associated with significant decreases in resistin, DKK-1, 11-dehydro-TXB2 and 8-iso-PGF2α, in parallel with HOMA decrease. In conclusion, resistin, antagonising insulin action in part through PPARγ activation, may favour insulin resistance and enhance oxidative stress, endothelial dysfunction and platelet activation. The adipokine-platelet interactions may be involved in platelet insulin resistance and their consequent pro-aggregatory phenotype in this setting.
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Del Ben, M., L. Polimeni, F. Baratta, S. Bartimoccia, R. Carnevale, L. Loffredo, P. Pignatelli, F. Violi y F. Angelico. "Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver". International Journal of Hepatology 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/784985.
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Background & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the association of oxidative stress with cytokeratin-18 M30 fragment levels, a marker of hepatocyte apoptosis.Methods.Steatosis severity was defined according to Hamaguchi’s echographic criteria in 209 patients with nonalcoholic fatty liver. Serum cytokeratin-18, urinary 8-iso-prostaglandin F2α, soluble NOX2-derived peptide, and adiponectin were measured.Results.Serum cytokeratin-18 progressively increased with steatosis severity (from 169.5 (129.3/183.8) to 176 (140/190) and 180 (169.5/192.5)μIU/mL in mild, moderate, and severe steatosis, respectively;P<0.01). After stratification by cytokeratin-18 tertiles, a significant progression of body mass index, HOMA-IR, triglycerides, urinary 8-iso-PGF2α, soluble NOX2-derived peptide, and of the prevalence of diabetes and severe steatosis was found, while HDL-cholesterol and adiponectin progressively decreased. A positive correlation between cytokeratin-18 and body mass index, HOMA-IR, Hamaguchi’s score, urinary 8-iso-PGF2α, and soluble NOX2-derived peptide and a negative correlation between cytokeratin-18 and HDL-cholesterol and adiponectin were found. Body mass index, adiponectin, and soluble NOX2-derived peptide were independent predictors of serum cytokeratin-18 levels (adjustedR2=0.36).Conclusion.We support an association between oxidative stress and severity of liver damage in patients with nonalcoholic fatty liver.
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Guo, Shuren, Xiaohuan Mao, Yunmeng Yan, Yan Zhang y Liang Ming. "Changes of liver transcriptome profiles following oxidative stress in streptozotocin-induced diabetes in mice". PeerJ 8 (27 de mayo de 2020): e8983. http://dx.doi.org/10.7717/peerj.8983.
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Background Oxidative-stress (OS) was causal in the development of cell dysfunction and insulin resistance. Streptozotocin (STZ) was an alkylation agent that increased reactive oxygen species (ROS) levels. Here we aimed to explore the oxidative-stress and related RNAs in the liver of STZ-induced diabetic mice. Methods RNA-sequencing was performed using liver tissues from STZ induced diabetic mice and controls. Pathway and Gene Ontology (GO) analyses were utilized to annotate the target genes. The differentially expressed RNAs involved in the peroxisome pathway were validated by qRT-PCR. The glucose metabolite and OS markers were measured in the normal control (NC) and STZ-induced diabetic mellitus (DM) group. Results The levels of serum Fasting insulin, HbA1c, Malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) were significant higher in DM groups than NC group, while SOD activity decreased significantly in DM groups. We found 416 lncRNAs and 910 mRNAs were differentially expressed in the STZ-induced diabetic mice compared to the control group. OS associated RNAs were differentially expressed in the liver of STZ-induced diabetic mice. Conclusion This study confirmed that the OS was increased in the STZ-induced DM mice as evidenced by the increase of lipid peroxidation product MDA and 8-iso-PGF2α, identified aberrantly expressed lncRNAs and mRNAs in STZ-induced diabetic mice.
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Green, C. R., L. T. Watts, S. M. Kobus, G. I. Henderson, J. N. Reynolds y J. F. Brien. "Effects of chronic prenatal ethanol exposure on mitochondrial glutathione and 8-iso-prostaglandin F2α concentrations in the hippocampus of the perinatal guinea pig". Reproduction, Fertility and Development 18, n.º 5 (2006): 517. http://dx.doi.org/10.1071/rd05128.
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It is hypothesised that oxidative stress is a key mechanism of ethanol neurobehavioural teratogenicity, resulting in altered endogenous antioxidant status and increased membrane lipid peroxidation in the hippocampus of chronic prenatal ethanol exposure (CPEE) offspring. To test this hypothesis, timed pregnant guinea-pigs (term, approximately gestational day (GD) 68) received chronic daily oral administration of (i) 4 g ethanol kg–1 maternal bodyweight, (ii) isocaloric sucrose with pair feeding, or (iii) water. At GD 65 (term fetus) and postnatal day (PD) 0 (neonate), individual offspring were killed, the brain was excised and the hippocampi were dissected. Glutathione (GSH) concentration was measured in the cytosolic and mitochondrial fractions of hippocampal homogenate. The occurrence of lipid peroxidation was determined by measuring the concentration of 8-iso-prostaglandin F2α (8-iso-PGF2α). There was CPEE-induced decreased brain weight and hippocampal weight at GD 65 and PD 0, decreased mitochondrial GSH concentration in the hippocampus at PD 0, with no change in mitochondrial GSH concentration at GD 65 or cytosolic GSH concentration at GD 65 or PD 0, and no change in mitochondrial or whole-homogenate 8-iso-PGF2α concentration in the hippocampus at GD 65 or PD 0. The data demonstrate that CPEE produces selective mitochondrial dysfunction in the hippocampus of the neonatal guinea-pig, involving GSH depletion.
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Sametz, Wolfgang, Simone Hennerbichler, Sonja Glaser, Reinhold Wintersteiger y Heinz Juan. "Characterization of prostanoid receptors mediating actions of the isoprostanes, 8-iso-PGE2 and 8-iso-PGF2α , in some isolated smooth muscle preparations". British Journal of Pharmacology 130, n.º 8 (agosto de 2000): 1903–10. http://dx.doi.org/10.1038/sj.bjp.0703522.
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