Serum 8-isoprostane Research Articles

The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study.

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.

DNA damage in inhabitants exposed to heavy metals near Hudiara drain, Lahore, Pakistan

The current study was conducted on the inhabitants living in the area adjacent to the Hudiara drain using bore water and vegetables adjacent to the Hudiara drain. Toxic heavy metals badly affect human health because of industrial environmental contamination. Particularly hundreds of millions of individuals globally have faced the consequences of consuming water and food tainted with pollutants. Concentrations of heavy metals in human blood were elevated in Hudiara drainings in Lahore city, Pakistan, due to highly polluted industrial effluents. The study determined the health effects of high levels of heavy metals (Cd, Cu, Zn, Fe, Pb, Ni, Hg, Cr) on residents of the Hudiara draining area, including serum MDA, 8-Isoprostane, 8-hydroxyguanosine, and creatinine levels. An absorption spectrophotometer was used to determine heavy metals in wate water, drinking water, soil, plants and human beings blood sampleas and ELISA kits were used to assess the level of 8-hydroxyguanosine, MDA, 8-Isoprostane in plasma serum creatinine level. Waste water samples, irrigation water samples, drinking water samples, Soil samples, Plants samples and blood specimens of adult of different weights and ages were collected from the polluted area of the Hudiara drain (Laloo and Mohanwal), and control samples were obtained from the unpolluted site Sheiikhpura, 60 km away from the site. Toxic heavy metals in blood damage the cell membrane and DNA structures, increasing the 8-hydroxyguanosine, MDA, creatinine, and 8-Isoprostane. Toxic metals contaminated bore water and vegetables, resulting in increased levels of creatinine, MDA, Isoprostane, and 8-hydroxy-2-guanosine in the blood of inhabitants from the adjacent area Hudiara drain compared to the control group. In addition,. This study also investigated heavy metal concentrations in meat and milk samples from buffaloes, cows, and goats. In meat, cow samples showed the highest Cd, Cu, Fe and Mn concentrations. In milk also, cows exhibited elevated Cu and Fe levels compared to goats. The results highlight species-specific variations in heavy metal accumulation, emphasizing the need for targeted monitoring to address potential health risks. The significant difference between the two groups i.e., the control group and the affected group, in all traits of the respondents (weight, age, heavy metal values MDA, 8-Isoprostane, 8-hydroxyguaniosine, and serum creatinine level). Pearson’s correlation coefficient was calculated. The study has shown that the level of serum MDA, 8-Isoprostane, 8-hydroxyguaniosine, or creatinine has not significantly correlated with age, so it is independent of age. This study has proved that in Pakistan, the selected area of Lahore in the villages of Laloo and Mohanwal, excess of heavy metals in the human body damages the DNA and increases the level of 8-Isoprostane, MDA, creatinine, and 8-hydroxyguaniosine. As a result, National and international cooperation must take major steps to control exposure to heavy metals.

Relation of Plasma Catecholamine Concentrations and Myocardial Mitochondrial Respiratory Activity in Anesthetized and Mechanically Ventilated, Cardiovascular Healthy Swine.

Chronic heart failure is associated with reduced myocardial β-adrenergic receptor expression and mitochondrial function. Since these data coincide with increased plasma catecholamine levels, we investigated the relation between myocardial β-receptor expression and mitochondrial respiratory activity under conditions of physiological catecholamine concentrations. This post hoc analysis used material of a prospective randomized, controlled study on 12 sexually mature (age 20-24 weeks) Early Life Stress or control pigs (weaning at day 21 and 28-35 after birth, respectively) of either sex. Measurements in anesthetized, mechanically ventilated, and instrumented animals comprised serum catecholamine (liquid-chromatography/tandem-mass-spectrometry) and 8-isoprostane levels, whole blood superoxide anion concentrations (electron spin resonance), oxidative DNA strand breaks (tail moment in the "comet assay"), post mortem cardiac tissue mitochondrial respiration, and immunohistochemistry (β2-adrenoreceptor, mitochondrial respiration complex, and nitrotyrosine expression). Catecholamine concentrations were inversely related to myocardial mitochondrial respiratory activity and β2-adrenoceptor expression, whereas there was no relation to mitochondrial respiratory complex expression. Except for a significant, direct, non-linear relation between DNA damage and noradrenaline levels, catecholamine concentrations were unrelated to markers of oxidative stress. The present study suggests that physiological variations of the plasma catecholamine concentrations, e.g., due to physical and/or psychological stress, may affect cardiac β2-adrenoceptor expression and mitochondrial respiration.

Low Grade Endotoxemia and Oxidative Stress in Offspring of Patients with Early Myocardial Infarction.

Background and aims: Offspring of patients with early myocardial infarction are at higher cardiovascular risk, but the underlying physio-pathological mechanism is unclear. NADPH oxidase-type 2 (NOX-2) plays a pivotal role as mediator of oxidative stress and could be involved in activating platelets in these patients. Furthermore, altered intestinal permeability and serum lipopolysaccharide (LPS) could be a trigger to promote NOX-2 activation and platelet aggregation. This study aims to evaluate the behavior of low grade endotoxemia, oxidative stress and platelet activation in offspring of patients with early myocardial infarction. Methods: We enrolled, in a cross-sectional study, 46 offspring of patients with early myocardial infarction and 86 healthy subjects (HS). LPS levels and gut permeability (assessed by zonulin), oxidative stress (assessed by serum NOX-2-derived peptide (sNOX2-dp) release, hydrogen peroxide (H2O2) production and isoprostanes), serum nitric oxide (NO) bioavailability and platelet activation (by serum thromboxane B2 (TXB2) and soluble P-Selectin (sP-Selectin)) were analyzed. Results: Compared to HS, offspring of patients with early myocardial infarction had higher values of LPS, zonulin, serum isoprostanes, sNOX2-dp H2O2, TXB2, p-selectin and lower NO bioavailability. Logistic regression analysis showed that the variables associated with offspring of patients with early myocardial infarction were LPS, TXB2 and isoprostanes. The multiple linear regression analysis confirmed that serum NOX-2, isoprostanes, p-selectin and H2O2 levels were significantly associated to LPS. Furthermore, serum LPS, isoprostanes and TXB2 levels were significantly associated with sNOX-2-dp. Conclusions: Offspring of patients with early myocardial infarction have a low grade endotoxemia that could generate oxidative stress and platelet activation increasing their cardiovascular risk. Future studies are needed to understand the role of dysbiosis in this population.

Effects of a Saccharomyces cerevisiae fermentation product-supplemented diet on fecal characteristics, oxidative stress, and blood gene expression of adult dogs undergoing transport stress.

Previously, a Saccharomyces cerevisiae fermentation product (SCFP) was shown to positively alter fecal microbiota, fecal metabolites, oxidative stress, and circulating immune cell function of adult dogs. The objective of this study was to measure the effects of SCFP on fecal characteristics, serum oxidative stress biomarkers, and whole blood gene expression of dogs undergoing transport stress. Sixteen adult pointer dogs [8M, 8F; mean age = 6.7 ± 2.1 yr; mean body weight (BW) = 25.5 ± 3.9 kg] were used in a randomized crossover design study. All dogs were fed a control diet for 4 wk, then randomly assigned to a control or SCFP-supplemented diet (formulated to include approximately 0.13% of the active SCFP ingredient) and fed to maintain BW for 11 wk. A 6-wk washout preceded the second 11-wk experimental period with dogs receiving opposite treatments. After 11 wk, fresh fecal and blood samples were collected before and after transport in a van for 45 min. Change from baseline data (i.e., before and after transport) were analyzed using the Mixed Models procedure of SAS 9.4, with P < 0.05 being significant and P < 0.10 being trends. Change in serum malondialdehyde concentrations increased (P < 0.05) and serum 8-isoprostane concentrations tended to increase (P < 0.10) in dogs fed SCFP, but decreased (P < 0.05) in control dogs after transport. Other serum markers were unaffected by diet during transport stress. Fecal dry matter percentage tended to be affected (P < 0.10) by diet during transport stress, being reduced in control dogs, but stable in dogs fed SCFP. Other fecal characteristics were unaffected by diet during transport stress. Genes associated with activation of innate immunity were impacted by diet in response to transport stress, with blood cyclooxygenase-2 and malondialdehyde mRNA expression being increased (P < 0.05) in control dogs, but stable or decreased in dogs fed SCFP. Expression of other genes was unaffected by diet during transport stress. These data suggest that the benefits of feeding a SCFP during transport stress may be mediated through suppression of innate immune cell activation.

123 Effects of a Saccharomyces Cerevisiae Fermentation Product-Supplemented Diet on Fecal Characteristics, Oxidative Stress, and Blood Gene Expression of Adult Dogs Undergoing Transport Stress

Abstract Previously, a Saccharomyces cerevisiae fermentation product (SCFP) was shown to positively alter fecal microbiota, fecal metabolites, and circulating immune cell function of adult dogs. The objective of this study was to measure the effects of SCFP on fecal characteristics, serum oxidative stress biomarkers, and whole blood gene expression of adult dogs undergoing transport stress. Sixteen adult pointer dogs (8M, 8F; mean age = 8.35 y; mean BW = 27.13 kg) were used in a randomized crossover design study. All dogs were fed control diet for 4 wk, then randomly assigned to a control or SCFP-supplemented diet and fed to maintain BW for 11 wk. A 6-wk washout preceded the second 11-wk experimental period with dogs receiving opposite treatments. After 11 wk, fresh fecal and blood samples were collected before and after transport in a van for 45 min. Change from baseline data (i.e., before and after transport) were analyzed using the Mixed Models procedure of SAS 9.4, with P&amp;lt; 0.05 being significant and P&amp;lt; 0.10 being trends. Changes in serum malondialdehyde and 8-isoprostane:creatinine concentrations increased (P&amp;lt; 0.05) in dogs fed SCFP, but decreased in control dogs with transport stress. Other serum markers were unaffected by diet during transport stress. Fecal dry matter percentage tended to be affected (P&amp;lt; 0.10) by diet during transport stress, being reduced in control dogs, but stable in dogs fed SCFP. Other fecal characteristics were unaffected by diet during transport stress. Blood cyclooxgenase-2 and myeloperoxidase mRNA expression was affected (P&amp;lt; 0.05) by diet during transport stress, being increased in control dogs, but stable or decreased in dogs fed SCFP. Expression of other genes was unaffected by diet during transport stress. These data suggest that the benefits of feeding a SCFP in a novel transport stress model are mediated more so by suppressing innate immune cell activation than through decreasing lipid peroxidation.

Elevated 8-isoprostane concentration is associated with thromboembolic events in patients with atrial fibrillation

BackgroundEnhanced oxidative stress occurs in atrial fibrillation (AF), however its impact on the efficacy and safety of anticoagulation is unknown. We sought to evaluate whether 8-isoprostaglandin F2 (8-isoprostane) levels are associated with clinical outcomes in anticoagulated AF patients. MethodsIn a study involving 243 AF patients (median age 69 years), we measured serum 8-isoprostane, along with prothrombotic markers, including plasma fibrin clot permeability, clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF), and fibrinolytic proteins. Ischemic cerebrovascular events, major bleeding, and death were recorded during a median follow-up of 53 months while on anticoagulation, largely on non-vitamin K antagonist oral anticoagulants (NOACs). ResultsIncreased 8-isoprostane levels were observed in women, in patients with arterial hypertension, and those with paroxysmal or persistent AF. Patients with 8-isoprostane levels ≥559 pg/mL (the top quartile) compared with those with 8-isoprostane <250 pg/mL (the bottom quartile) had higher fibrinogen, lower VWF, higher plasminogen activator inhibitor 1, along with lower fibrin clot permeability with no difference in CHA2DS2-VASc score, CLT or ETP. Patients who experienced thromboembolic events (n = 20, 1.9%/year) had 48.6% higher 8-isoprostane concentrations compared to the remainder (P <0.01). Levels of 8-isoprostane >459 pg/mL based on the optimal cut-off value were associated with thromboembolic events during follow-up (hazard ratio 2.87, 95% confidence interval 1.17–7.03, P = 0.02). There were no associations between 8-isoprostane and major bleeding (2.0%/year) or all-cause mortality (1.9%/year). ConclusionsIncreased 8-isoprostane levels partly through altered fibrin clot structure are associated with thromboembolic events despite anticoagulant therapy in AF patients.

Коморбідність хронічного обструктивного захворювання легень та артеріальної гіпертензії: залежність між показниками оксидативного стресу та функції зовнішнього дихання

Introduction. Hypertension (AH) is considered to be one of the major comorbidities associated with chronic obstructive pulmonary disease (COPD). The pathogenesis of COPD, like hypertension, is closely related to oxidative stress. The question of the influence of the changes developing against the background of the studied comorbidity on the indicators of the function of external respiration remains important. The aim of this study – to establish the relationship between the indicators of free radical oxidation and the function of external respiration in the combined course of chronic obstructive pulmonary disease and hypertension. Materials and methods. The study included 53 patients with COPD, 28 of whom had comorbid hypertension, stage 1. Spirography was performed on a Spirolab III (Germany). DCFH-DA (dichlorodihydrofluorescein diacetate), a specific test for the detection of hydrogen peroxide (H2O2), and DHE (dichloroetidium), which detects anion-radical superoxide (O2 • -), were determined on a flow cytometer USICman X EP. Serum 8-isoprostane levels were measured by enzyme-linked immunosorbent assay. Research results and their discussion. In patients with COPD, as well as with the comorbidity of COPD + hypertension, a relationship was found between the expression of oxidative stress and indicators of respiratory function. Thus, in patients of both study groups, high values of H2O2, O2•- and 8-isoprostane were significantly associated with low spirographic values, which indicated bronchial obstruction. The indicators of oxidative stress were statistically significantly inversely correlated with the values that characterize the patency of the large and medium bronchi (MOS 25 and MOS 50). Conclusions. In patients with a combined course of COPD and hypertension, there was a relationship between the expression of oxidative stress and indicators of respiratory function, which was characterized by the association of high values of free radical oxidation with low spirographic indicators (hydrogen peroxide-FEV1 = -0.55; O2•- -FEV1 = 0.33; 8-isoprostane-FEV1 = -0.51), which indicate bronchial obstruction.

Protective properties of sardine and chickpea protein hydrolysates against lipoprotein oxidative damages and some inflammation markers in hypercholesterolemic rats

OBJECTIVE: This study evaluated the effect of sardine (SPH) and chickpea protein hydrolysates (CPH) on oxidant stress and inflammatory profile in cholesterol-fed rats. METHODS: The experiment was undertaken for thirty days on 18 cholesterol-fed Wistar rats (220±10 g) divided into three groups and receiving 1 g/kg of body weight either chickpea protein hydrolysate (CPH), sardine protein hydrolysate (SPH) or casein in water (CG). RESULTS: Compared to CG, SPH and CPH treatment reduced cholesterol, hydroperoxide and malondialdehyde contents in serum, lipoproteins, erythrocytes and aorta. These same treated groups showed also lower serum isoprostane levels. However, serum paraoxonase activity and HDL-antioxidant property were improved only by CPH compared to CG. SOD activity of aorta and erythrocytes was higher in CPH but in SPH group, SOD activity was lower in these tissues and remained unchanged in serum. Furthermore, CPH and SPH stimulated glutathione peroxidase and catalase activities of aorta and erythrocytes. In CPH group, nitric oxide levels of serum, erythrocytes and aorta were increased by respectively 1.4- to 1.8-fold compared to CG and SPH. In addition, among the three groups, CPH exhibited the best anti-inflammatory effect by lowering serum C reactive protein, uric acid and albumin concentrations. CONCLUSIONS: SPH and particularly CPH possess antioxidant and anti-inflammatory properties and could be useful as nutraceuticals for health improving and preventing numerous disorders such as cardiovascular diseases.

Hepatoprotective and Anti-Obesity Properties of Sardine By-Product Oil in Rats Fed a High-Fat Diet.

Excess lipid intake can trigger liver lipid accumulation and oxidative responses, which can lead to metabolic disturbances and contribute to hepatic steatosis and obesity and increase the risk of cardiovascular disease. Production of fish oil rich in omega-3 is a good opportunity for valorizing fish by-products in the therapeutic field. In this study, we explored the effects of oil from Sardina pilchardus by-products on cardiometabolic and oxidative disorders caused by toxic effects of excess lipids in obese rats. Three groups of obese rats received either 20% sardine by-product oil (SBy-Ob-HS; experimental group), 20% fillet oil (SF-Ob-HS; positive control group), or a high-fat diet (Ob-HS). Normal weight rats received a standard diet (normal). There was a significant decrease in serum total cholesterol (TC), triacylglycerols (TG), and insulin concentrations in the SBy-Ob-HS group compared with the SF-Ob-HS group. Compared with the Ob-HS group, TC and TG, glycemia, glycosylated hemoglobin, and insulinemia were decreased in the SBy-Ob-HS (more notably) and SF-Ob-HS groups. Furthermore, hepatic lipids, low density lipoprotein-cholesterol (C), the non-esterified cholesterol/phos-pholipids ratio, serum transaminases activities and lipid peroxidation were lower and serum high density lipoproteins-C were higher in the SBy-Ob-HS and SF-Ob-HS groups compared with the Ob-HS group. Serum isoprostane concentrations were reduced in the SBy-Ob-HS (more notably) and SF-Ob-HS groups compared with the Ob-HS and normal groups. The activities of antioxidant enzymes in tissues were enhanced, particularly in the by-product oil group. The oil extracted from by-products demonstrate anti-obesity properties (hypolipemiant, hepatoprotective, antiatherogenic, antidiabetic, and antioxidant) that may be beneficial for the management of obesity and its complications, such as hepatic steatosis.

Serum 8-isoprostane levels in patients with resistant oral lichen planus before and after treatment with lycopene: a randomized clinical trial

BackgroundOral lichen planus is an autoimmune disease in which topical steroids are the first line of treatment. The adverse effects of systemic corticosteroids prescribed for resistant oral lichen planus cases advocate alternative modalities. Lycopene is an antioxidant with a wide range of beneficial properties. This trial aimed to evaluate the effect of pure lycopene as compared to systemic corticosteroids (Prednisolone) on the symptoms, signs and oxidative stress in patients with erosive oral lichen planus recalcitrant to topical steroids.MethodsTwenty patients were randomly divided into the test (lycopene) and control (corticosteroids) groups. Numeric rating scale and Escudier et al. (Br J Dermatol 4:765–770, 2007. https://doi.org/10.1111/j.1365-2133.2007.08106.x) lesion scores were assessed at baseline and weeks 4 and 8 from baseline. Serum levels of 8-isoprostane were measured in all patients at baseline and at the end of treatment (week 8).ResultsThere was a significant reduction in signs and symptoms after the end of treatment in each group. However, no significant difference was found between the lycopene and the corticosteroids group. Moreover, a significant reduction in 8-isoprostane levels was observed in the lycopene group from baseline and as compared to the control group.ConclusionsBased on the study results, lycopene is a safe and effective therapeutic modality for resistant oral lichen planus. 8-isoprostane is a biomarker of lipid peroxidation that can be reduced by lycopene.Trial registration ID: PACTR202003484099670. 'Retrospectively registered on 11/3/2020'.

Nitrite and tempol combination promotes synergic effects and alleviates right ventricular wall stress during acute pulmonary thromboembolism

IntroductionThe mechanical obstruction and pulmonary vasoconstriction are major determinants of the sudden right ventricular (RV) afterload increases observed during acute pulmonary thromboembolism (APT). Vasodilators and antioxidants agents have been shown to mitigate pulmonary hypertension. We examined whether sodium nitrite and the antioxidant tempol combination could be advantageous in an APT sheep model. MethodsAPT was induced in anesthetized sheep by autologous blood clots (250 mg/kg) into the right atrium. Thirty minutes after APT induction, the animals received a continuous infusion of tempol (1.0 mg/kg/min), increasing sodium nitrite infusion (5, 15, and 50 μmol/kg), or a simultaneous combination of both drugs. Saline was used as a control treatment. Hemodynamic measurements were carried out every 15 min. Also, whole blood nitrite and serum 8-isoprostanes levels were measured. ResultsAPT induced sustained pulmonary hypertension, increased dp/dtmax, and rate pressure product (RPP). Nitrite or tempol treatments attenuated these increases (P < 0.05). When both drugs were combined, we found a robust reduction in the RV RPP compared with the treatments alone (P < 0.05). The sole nitrite infusion increased blood nitrite concentrations by 35 ± 6 μM (P < 0.05), whereas the nitrite and tempol combination produced higher blood nitrite concentrations by approximately 54 ± 7 μM. Tempol or nitrite infusions, both alone or combined, blunted the increases in 8-isoprostane concentrations observed after APT. ConclusionsNitrite and tempol combination protects against APT-induced RV wall stress. The association of both drugs may offer an advantage to treat RV failure during severe APT.

Immune activation and arterial stiffness in lean adults with HIV on antiretroviral therapy.

BackgroundGreater T-cell activation was associated with reduced vascular compliance amongst persons living with HIV (PLWH) especially among overweight and obese individuals. There is a paucity of data regarding immune activation and arterial stiffness amongst PLWH in sub-Saharan Africa (SSA).ObjectiveTo determine the association between immune activation and arterial stiffness in lean PLWH in SSA.MethodForty-eight human immunodeficiency virus positive (HIV+) adults on antiretroviral therapy (ART) >5 years and 26 HIV-negative adults, all with BMI < 25 kg/m2 and no history of CVD, were enrolled. The relationship of vascular compliance with circulating CD4+ and CD8+ naïve, memory, activated and senescent T cells, and serum 8-isoprostane was assessed by HIV status.ResultsIncreased immune activation was observed in the CD4+ and CD8+ T cells of PLWH, 16.7% vs. 8.9% and 22.0% vs. 12.4% respectively; p < 0.001 (both). Furthermore, a higher proportion of senescent CD4+ T cells were associated with a lower carotid-femoral pulse wave velocity (cfPWV; p = 0.01), whilst a higher proportion of activated CD8+ T cells were associated with a lower carotid-radial pulse wave velocity (crPWV; p = 0.04), after adjustment for BMI and age. However, PLWH also had a higher median carotid-femoral augmentation index (cfAiX) (21.1% vs. 6.0%; p < 0.05) in comparison to their HIV controls.ConclusionOur population of lean PLWH had increased immune activation and higher cfAiX, a marker of arterial stiffness, compared to HIV-negative persons. The negative association between immune activation and arterial stiffness as measured by crPWV in PLHW on long-term treatment needs further elucidation.

Maternal serum nitrotyrosine, 8-isoprostane and total antioxidant capacity levels in pre-gestational or gestational diabetes mellitus

Objective To evaluate serum concentration of 8-isoprostane, nitrotyrosine (NT), and total antioxidant capacity (TAC) in pregnant women with diabetes mellitus (DM) considering preconception planning and method of diabetes correction in 11–14 and 30–34 weeks. Materials and methods The study included 130 women: T1DM (n = 40), T2DM (n = 35), gestational diabetes (GDM, n = 40) and the control group (n = 15). The serum concentrations of NT, 8-isoprostane, and TAC were measured by ELISA methods. Results Elevated 8-isoprostane levels were observed in all patients with DM, but this biomarker's maximum values have been seen in T1DM and T2DM on insulin groups. A similar tendency was observed for the concentration of NT in both the 1st and 3rd trimesters. TAC levels showed a statistically relevant decrease in all DM groups compared to the control. The correlation analysis showed a direct correlation between HbA1c and serum 8-isoprostane levels in the 1st (r = .27) and 3rd (r = .3) pregnancy trimesters as well as inverse correlation with TAC level (r = −.48). Direct (NT, 8-isoprostane) and inverse correlations (TAC) were fixated for this biomarker concentration and preeclampsia rates. Conclusion DM in pregnancy is related to oxidative stress activation, which might lead to the development of adverse perinatal outcomes.

The correlation of fetal cardiac function with gestational diabetes mellitus (GDM) and oxidative stress levels.

Background The primary objective of this study was to compare the fetal cardiac performance index (Tei index) between the fetuses of gestational diabetes mellitus (GDM) mothers and non-GDM mothers; and the secondary objective was to compare various other parameters of fetal cardiac function as well as maternal oxidative stress levels between the groups of GDM and non-GDM mothers. Methods A cross-sectional study was conducted on pregnant women at 24-28 weeks of gestation. All of the participants underwent 100 g, 3-h oral glucose tolerance test (OGTT) as a diagnostic test for GDM and were categorized as non-GDM and GDM group. All participants had fetal echocardiography performed for cardiac function, and then maternal blood samples were collected for biomarker measurements. Results A total of 80 pregnant women, including 43 in the GDM group and 37 in the non-GDM group, were included in the study. The maternal serum 8-isoprostane (8IsoP), tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 levels were significantly higher in the GDM group than those in the non-GDM group (P: 0.028, P: 0.019 and P: 0.031, respectively). The fetal cardiac function parameters were not significantly different between the two groups. Regardless of the GDM status, the fetuses with high levels of oxidative stress (8Isop ≥1000 pg/mg protein) had a significantly higher rate of impaired shortening fraction (SF) of the left ventricle (P: 0.001). Conclusion GDM is significantly associated with an increase in the oxidative stress process, and a high level of oxidative stress was significantly associated with left ventricular (LV) function impairment. Though a correlation between GDM and fetal cardiac function impairment was not clearly demonstrated in this study, this study suggests that GDM patients with a high level of oxidative stress should be evaluated for fetal cardiac function.

N-acetylcysteine Restored Heart Rate Variability and Prevented Serious Adverse Events in Transfusion-dependent Thalassemia Patients: a Double-blind Single Center Randomized Controlled Trial.

Regular blood transfusions in transfusion-dependent thalassemia (TDT) patients can lead to iron overload, causing oxidative stress and sympathovagal imbalance, resulting in increased cardiac complications. We hypothesized that administrating of N-acetylcysteine (NAC) prevents serious adverse events including cardiac complications in TDT patients by reducing systemic oxidative stress and balancing cardiac sympathovagal control. This study was double-blind, randomized control trial, investigating in 59 Thai TDT patients. After randomization, the participants were divided into two groups. The control group received standard care of TDT patient plus placebo, whereas the intervention group received 600 mg of NAC orally for six months. Serum 8-isoprostane, TNF-alpha, IL-10, 24-hour ECG monitoring, echocardiograms and the incidence of thalassemia-related complications were collected. At baseline, no significant difference in any parameters between the control and the intervention groups. At the end of intervention, the incidence of serious adverse events (i.e. infection, worsening thalassemia) was significantly higher in the control group when compared with the intervention group (24.1% vs. 3.3%, p=0.019) (Chi-square test; absolute risk reduction=20.8%, number needed to treat=4.8). The control group also had significantly lower time-dependent HRV parameters, compared with the intervention group (p=0.025 and 0.030, independent t-test). Treatment with NAC restored HRV and reduced serious adverse event in TDT patients, however, no difference in cardiac complications could be demonstrated. NAC could prevent serious adverse events in TDT patients. The proposed mechanism might be the balancing of sympathovagal control.

Enhanced NOX-2 derived oxidative stress in offspring of patients with early myocardial infarction

BackgroundOffspring of patients with early myocardial infarction have a higher risk to develop cardiovascular events; the underlying physiopathology is still unclear. Several lines of evidence support a role for oxidative stress in atherogenesis and NADPH oxidase-2 (NOX-2) is considered a major source of O2– in human. Furthermore, oxidative stress regulates arachidonic acid metabolism via activation of platelet phospholipase-A2.The aim of this study was to address NOX-2 activity as well as serum thromboxane B2 (TXB2) and 8-isoPGF2-alpha in offspring of patients with premature myocardial infarction. MethodsNinety-two consecutive subjects, including 46 offspring of patients with premature myocardial infarction and 46 healthy subjects (HS) matched for age and gender, were recruited.A cross sectional study was performed to compare serum activity of soluble NOX-2-dp (sNOX-2-dp), blood levels of isoprostanes and serum TXB2 in these two groups. ResultsCompared with HS, offspring of patients with early myocardial infarction had higher values of serum TxB2, isoprostanes and sNOX-2-dp. Bivariate analysis in the overall population showed that serum sNOX-2-dp levels were significantly associated with serum isoprostanes and TXB2. A multiple linear regression analysis was performed to define the independent predictors of sNOX-2-dp. Serum isoprostanes (SE: 0.07; standardized coefficient β: 0.579; P < 0.001) and TXB2 levels (SE: 0.06; standardized coefficient β: 0.211; P < 0.001) were significantly associated to sNOX-2-dp (R2: 0.42). ConclusionThis study shows that Nox-2 activation is a key determinant of oxidative stress and platelet activation in offspring of patients with premature myocardial infarction.

Hazelnut and cocoa spread improves flow-mediated dilatation in smokers.

Hazelnut and cocoa spread is an Italian product containing cocoa and hazelnut. Several epidemiological studies suggest that cocoa and hazelnuts cocoa exert beneficial cardiovascular effects. To investigate whether in smokers, hazelnut and cocoa spread elicits artery dilatation via down-regulation of oxidative stress. Flow-mediated dilatation (FMD), oxidative stress (as assessed by serum isoprostanes excretion, Nox2 activation and NO bioavailability) and antioxidant status [as assessed by vitamin E levels, plasma total polyphenols and H2O2 breaking down activity (HBA)] were studied in 20 smokers in a crossover, single-blind study. Patients were randomly allocated to 60g of Hazelnut and cocoa spread or 60g of milk chocolate (≤ 35% cocoa). FMD, serum isoprostanes, Nox2 activation, NOx, vitamin E, HBA and total polyphenols were assessed at baseline and 2h after chocolate ingestion. After Hazelnut and cocoa spread intake, FMD and NOx significantly increased (from 4.3 ± 2.8 to 8.0 ± 3.2%, p < 0.001 and from 23.1 ± 5.5 to 32.0 ± 12.6µM, p = 0.016, respectively); conversely, serum isoprostanes and Nox2 activation significantly decreased (from 302.8 ± 59.8 to 240.7 ± 90.8pmol/l, p = 0.03 and from 25 ± 4.4 to 22.6 ± 3.2, p = 0.03, respectively). After Hazelnut and cocoa spread intake, serum total polyphenols, vitamin E and HBA significantly increased (from 133.8 ± 49.7 to 202.5 ± 69.5mg/l GAE, p = 0.001; from 3.56 ± 1.4 to 4.5 ± 1.0μmol/mmol cholesterol, p = 0.002 and from 63.3 ± 13.2 to 74.2 ± 12.4%, p = 0.003, respectively). No changes in the above variables were observed after milk chocolate intake. A linear correlation analysis shows that Δ (expressed by difference of values between before and after chocolate intake) of FMD correlates with Δ of total polyphenols and Δ of vitamin E. This study shows that Hazelnut and cocoa spread improves FMD with a mechanism potentially involving downregulation of oxidative stress and eventually increased NO generation in smokers.

The Effect of Resistance Training with Moderate and Progressive Intensity on Indices of Oxidative Stress (Serum 8-Isoprostane, Malondialdehyde and Reduced Glutathione Levels) in Young Healthy Men

Background: 8-isoprostane(8-IsoP) and malondialdehyde (MDA) are novel and classic index of lipid per oxidation, respectively, and reduced glutathione (GSH) is an index of antioxidant status, which the chronic adaptation of moderate and progressive resistance training on them is unclear. The purpose of this study is to investigate and compare the effect of 9 weeks moderate and progressive resistance training on serum 8-isoprostane, malondialdehyde and reduced glutathione levels in young men (from 17- to 21 year-olds). Methods: In the semi-experimental study, 36 volunteers were randomly divided in to 3 groups of 12 men involving: moderate and progressive resistance training and control groups. The training protocol involved three periods of three weeks each with progressive intensity. The moderate training group performed the first period of protocol in throughout of study (just 5 percent increase in training intensity as overload), while the training load of progressive training group was incrementally increased in every period. Blood sampling were taken in two phases involving pre test and following ninth week from anterior brachial vein. The variables were measured via sandwich ELISA. Results: The results of ANCOVA and Bonferroni tests showed that 9 weeks of moderate and progressive resistance training led to significance decrease in lipid oxidation indices (8-IsoP and MDA);the range of the decline especially in serum 8-IsoP was more in progressive group. Significant change in serum GSH levels was not observed in the training groups. Conclusions: The results of this study show that periodic increase in resistance training load leads to improves in oxidative stress adaptability. Moreover, 8-IsoP is more accurate index for predicting oxidative stress compared to MDA.

Isoprostane in systemic sclerosis: A systematic review and meta-analysis

Objectives: To further the knowledge of oxidative stress in systemic sclerosis (SSc), we performed a systematic review and meta-analysis on studies measuring isoprostane, a vasoactive agent deriving from arachidonic acid and implicated in the vasculopathy of SSc.Methods: Systematic search following the PRISMA guidelines in PubMed and EMBASE between January-1990/December-2017 using the terms: oxidative stress, isoprostane, systemic sclerosis and scleroderma.Results: After the screening process, 8 studies including 240 SSc patients and 192 controls were included in the systematic review and meta-analysis, 6 investigating urinary and 2 serum isoprostane: random effect meta-analysis revealed isoprostane overgeneration in SSc (p < .001) with wide heterogeneity (I2 = 75%). Subgroup analysis on urinary isoprostane favoured excess excretion in SSc (p = .009) with slightly lower heterogeneity (I2 = 67%); further subgroup analysis according to unit of measurement revealed no increased isoprostane excretion when expressed as pg/mg creatinine but increased when expressed as pmol/mmol creatinine (p = .05) with medium heterogeneity (I2 = 32%). Subgroup analysis on serum isoprostane favoured overproduction in SSc (p < .0001) with no heterogeneity.Conclusion: There is some evidence for isoprostane overgeneration in SSc that confirms the occurrence of oxidative stress in this setting: further prospective studies with specified outcomes are needed to evaluate the prognostic value of this functional biomarker.