Systemic Oxidative Stress Levels Research Articles

Systemic oxidative stress levels during the course of pregnancy: Associations with exposure to air pollutants

Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM2.5), and nitrogen dioxide (NO2). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM2.5, NO2, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2′-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM2.5 concentration (3.20 μg/m3) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2nd (−7.99%, 95% CI: 13.8%, −2.23%) or 3rd trimester (−2.81%, 95% CI: 10.0%, 4.38%). The average cumulative PM2.5 exposures in the 3–7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM2.5 concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO2 exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM2.5 and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.

Systemic Oxidative Stress Level as a Pathological and Prognostic Factor in Myopic Choroidal Neovascularization

PurposeTo investigate the association of oxidative stress level with myopic choroidal neovascularization (mCNV) and its clinical outcomes. DesignRetrospective case-control study. ParticipantsThis retrospective study included 52 eyes of 52 healthy participants (mean age 62.5 years), 30 eyes of 30 patients (mean age 59.6 years) with high myopia (HM) and no mCNV, and 23 eyes of 23 patients (mean age 61.8 years) with HM and mCNV who received intravitreal anti-vascular endothelial growth factor antibody injections (IVIs) with a pro re nata regimen for 6 months after an initial IVI. MethodsClinical findings, including oxidative stress parameters, such as diacron reactive oxygen metabolites (dROMs), biological antioxidant potential (BAP), and BAP/dROM ratio (B/d ratio), were analyzed. Main Outcome MeasuresClinical features and oxidative stress parameters. ResultsBoth BAP and B/d ratio were significantly lower in the HM/mCNV group than in the HM/no mCNV group (P=0.002 and P=0.012, respectively) or the control group (P=0.001 and P=0.026, respectively). In a multivariate logistic regression analysis (adjusted for age, gender, and axial length), B/d ratio (OR=0.47, P=0.026) was significantly associated with mCNV. Dividing the patients into high and low B/d ratio groups (with a cutoff of 5.2) showed that subfoveal choroidal thickness (SFCT) was lower (P=0.002) and the number of IVI treatments was higher (P=0.029) in eyes with a low B/d ratio than in eyes with a high B/d ratio. In a multiple regression analysis (adjusted for age, gender, and axial length), only B/d ratio was significantly associated with SFCT (β=0.68, P=0.006). ConclusionThe oxidative stress level in eyes with HM differed according to mCNV, SFCT, and the number of IVI treatments. Measuring oxidative stress parameters might be useful in eyes with HM both for assessing the risk of developing mCNV and determining disease activity.

The systemic oxidative stress score has a prognostic value on gastric cancer patients undergoing surgery.

Oxidative stress is strongly associated with the development, recurrence metastasis, and treatment of gastric cancer. It is yet unknown, though, how systemic oxidative stress levels relate to the surgically treated gastric cancer patients' clinical results. This research aims to investigate the prognostic effect of systemic oxidative stress score, also known as systematic oxidative stress score (SOS), on gastric cancer patients undergoing surgical treatment. Development of the SOS Formula through Least Absolute Shrinkage and Selection Operator LASSO Cox Regression. By using optimal cut-off values, the 466 patients included in the study had been split into high SOS and low SOS groups. Utilizing Chi-square test and the Wilcoxon rank sum test, this research examined the relationship between SOS and clinical traits. With the aid of Kaplan-Meier and COX regression analysis, the prognosis of patients with gastric cancer was examined. SOS consisted of four oxidative stress-related laboratory indices. Univariate and multivariate COX regression analyses revealed that SOS, Age, CA724, Radical resection and TNM stage were crucial prognostic factors for OS, and the independent prognostic factors for PFS included Age, CA724, TNM stage and SOS. They could have their prognosis correctly predicted using a nomogram built around SOS and independent prognostic variables. SOS is a practical and reasonably priced tool for determining a patient's prognosis for gastric cancer. More notably, SOS is an accurate prognostic factor for patients with advanced gastric cancer who has undergone radical surgery.

Luteolin Alleviates Oxidative Stress in Chronic Obstructive Pulmonary Disease Induced by Cigarette Smoke via Modulation of the TRPV1 and CYP2A13/NRF2 Signaling Pathways.

The current study aims to investigate the therapeutic potential of luteolin (Lut), a naturally occurring flavonoid found in various medicinal plants, for treating chronic obstructive pulmonary disease (COPD) through both in vitro and in vivo studies. The results demonstrated that Lut increased body weight, reduced lung tissue swelling and lung damage indices, mitigated systemic oxidative stress levels, and decreased alveolar fusion in cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced COPD mice. Additionally, Lut was observed to downregulate the expression of the TRPV1 and CYP2A13 proteins while upregulating SIRT6 and NRF2 protein expression in CS + LPS-induced COPD mice and cigarette smoke extract (CSE)-treated A549 cells. The concentrations of total reactive oxygen species (ROS) and mitochondrial ROS in A549 cells induced by CSE significantly increased. Moreover, CSE caused a notable elevation of intracellular Ca2+ levels in A549 cells. Importantly, Lut exhibited inhibitory effects on the inward flow of Ca2+ and attenuated the overproduction of mitochondrial and intracellular ROS in A549 cells treated with CSE. In conclusion, Lut demonstrated a protective role in alleviating oxidative stress and inflammation in CS + LPS-induced COPD mice and CSE-treated A549 cells by regulating TRPV1/SIRT6 and CYP2A13/NRF2 signaling pathways.

Air pollution and oxidative stress in adults suffering from airway diseases. Insights from the Gene Environment Interactions in Respiratory Diseases (GEIRD) multi-case control study

Air pollution is a leading risk factor for global mortality and morbidity. Oxidative stress is a key mechanism underlying air-pollution-mediated health effects, especially in the pathogenesis/exacerbation of airway impairments. However, evidence lacks on subgroups at higher risk of developing more severe outcomes in response to air pollution. This multi-centre study aims to evaluate the association between air pollution and oxidative stress in healthy adults and in patients affected by airway diseases from the Italian GEIRD (Gene Environment Interactions in Respiratory Diseases) multi-case control study. Overall, 1841 adults (49 % females, 20–83 years) were included from four Italian centres: Pavia, Sassari, Turin, and Verona. Following a 2-stage screening process, we identified 1273 cases of asthma, chronic bronchitis, rhinitis, or COPD and 568 controls. Systemic oxidative stress was quantified by urinary 8-isoprostane and 8-OH-dG. Individual residential exposures to NO2, PM10, PM2.5, and O3 were derived using an innovative five-stage machine-learning-based approach. Linear mixed regression models tested the association between oxidative stress biomarkers and air pollution tertiles, adjusting by age, sex, BMI, smoking, education and season, with recruiting centres as random intercept. Only cases exhibited higher levels of log-transformed 8-isoprostane and 8-OH-dG in association with NO2 (β: 0.30 95 % CI: 0.08–0.52 and 0.20 95 % CI: 0.03–0.37), PM10 (0.34 95 % CI: 0.12–0.55 and 0.21 95 % CI: 0.05–0.37) and PM2.5 (0.27 95 % CI: 0.09–0.49 and 0.18 95 % CI: 0.02–0.34) as compared to the first tertile of exposure. No significant associations were observed for summer O3. Our findings suggest that exposure to air pollution may increase systemic oxidative stress levels in people suffering from airway diseases. This introduces a potential novel approach available for future epidemiological studies and Public Health for effective prevention strategies oriented at the quantification of early biological effects in susceptible people, whose additional risk level might be currently underrated. Air-pollution-mediated exacerbations, driven by oxidative stress, still deserve our attention.

Oxidative stress biomarker triggered multiplexed tool for auxiliary diagnosis of atherosclerosis.

Oxidative stress is integral in the development of atherosclerosis, but knowledge of how oxidative stress affects atherosclerosis remains insufficient. Here, we design a multiplexed diagnostic tool that includes two functions (photoacoustic imaging and urinalysis), for assessing intraplaque and urinary malondialdehyde (MDA), a well-recognized end-product of oxidative stress. Molecular design is conducted to develop the first near-infrared MDA-responsive molecule (MRM). Acid-unlocked ratiometric photoacoustic nanoprobe is designed to report intraplaque MDA, enabling it to reflect plaque burden. Furthermore, MRM is tailored for urinary MDA detection with excellent specificity in a blind study. Moreover, we found a significant difference in urinary MDA between healthy adults and atherosclerotic patients (more than 600 participants). Combining these two functions, such a multiplexed diagnostic tool can dynamically report intraplaque and systemic oxidative stress levels during atherosclerosis progression, pneumonia infection, and drug treatment in atherosclerotic mice, which is promising for the auxiliary diagnosis of atherosclerosis.

Impact of Exercise Intensity on Systemic Oxidative Stress, Inflammatory Responses, and Sirtuin Levels in Healthy Male Volunteers.

Exercise can induce anti-inflammatory and antioxidant effects, for which regulation of sirtuins (SIRTs) may be a major consideration for exercise prescription. The purpose of this study was to investigate the effects of acute aerobic exercise, in particular its intensity, on systemic oxidative stress, inflammatory responses, and SIRT levels. Twenty healthy, untrained males were recruited and randomly assigned to moderate-intensity (MI, 65% VO2max, n = 10) and high-intensity (HI, 85% VO2max, n = 10) exercise. Blood samples were obtained pre-, immediately post-, and 1 h post-exercise for measurements of malonaldehyde (MDA), superoxide dis-mutase (SOD), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, SIRT-1, SIRT-2, and SIRT-3. Overall, MDA, SOD, IL-6, SIRT-1, and SIRT-3 levels were significantly increased at post-exercise compared with pre-exercise regardless of exercise intensity (p < 0.05). The HI group had significantly higher MDA, SOD, and IL-6 levels than the MI group at post-exercise (p < 0.05), whereas no significant differences were observed in the IL-1β, TNF-α, and SIRT-2 levels (p > 0.05). Altogether, these findings suggest that exercise-induced oxidative stress and inflammatory responses may be dependent on exercise intensity. Moreover, activation of inflammatory cytokines and SIRT family members may be dependent on the intensity of the exercise.

The role of dynamic thiol/disulfide homeostasis for the evaluation of oxidative stress in endometriosis patients

Objective: To evaluate the role of oxidative stress in endometriosis patients by determining dynamic thiol/disulfide homeostasis and ischemia modified albumin (IMA) levels. Patients and Methods: This prospective case-controlled study was conducted at a tertiary gynecology clinic in Istanbul, Turkey. 86 patients previously diagnosed with endometriosis and persistent endometriomas were included in the study group. 60 patients who visited the clinic during the study period for routine gynecological control were included in the control group. Thiol/disulfide parameters and IMA levels were determined from the serum samples. Results: When the thiol/disulfide parameters were compared between the study and the control group no significant difference was observed (p=0.49). Mean disulfide level in the control group was 18.58 ± 5.73 μmol/L and in the study group was 18.61 ± 7.37 μmol/L. Levels were statistically similar in both groups (p=0.98). In addition, there were no differences between the groups in terms of IMA and albumin levels. Conclusion: The results of this study revealed no significant difference in the dynamic thiol/disulfide homeostasis among the endometriosis patients. Although, it has been accepted as a potential oxidative stress marker in other chronic inflammatory diseases, its use in determining the systemic oxidative stress level in endometriosis patients is limited.

Crucial Role of Stromal Interaction Molecule-Activated TRPC-ORAI Channels in Vascular Remodeling and Pulmonary Hypertension Induced by Intermittent Hypoxia.

Obstructive sleep apnea (OSA), a sleep breathing disorder featured by chronic intermittent hypoxia (CIH), is associate with pulmonary hypertension. Rats exposed to CIH develop lung vascular remodeling and pulmonary hypertension, which paralleled the upregulation of stromal interaction molecule (STIM)-activated TRPC-ORAI Ca2+ channels (STOC) in the lung, suggesting that STOC participate in the pulmonary vascular alterations. Accordingly, to evaluate the role played by STOC in pulmonary hypertension we studied whether the STOC blocker 2-aminoethoxydiphenyl borate (2-APB) may prevent the vascular remodeling and the pulmonary hypertension induced by CIH in a rat model of OSA. We assessed the effects of 2-APB on right ventricular systolic pressure (RVSP), pulmonary vascular remodeling, α-actin and proliferation marker Ki-67 levels in pulmonary arterial smooth muscle cells (PASMC), mRNA levels of STOC subunits, and systemic and pulmonary oxidative stress (TBARS) in male Sprague-Dawley (200 g) rats exposed to CIH (5% O2, 12 times/h for 8h) for 28 days. At 14 days of CIH, osmotic pumps containing 2-APB (10 mg/kg/day) or its vehicle were implanted and rats were kept for 2 more weeks in CIH. Exposure to CIH for 28 days raised RVSP > 35 mm Hg, increased the medial layer thickness and the levels of α-actin and Ki-67 in PASMC, and increased the gene expression of TRPC1, TRPC4, TRPC6 and ORAI1 subunits. Treatment with 2-APB prevented the raise in RVSP and the increment of the medial layer thickness, as well as the increased levels of α-actin and Ki-67 in PASMC, and the increased gene expression of STOC subunits. In addition, 2-APB did not reduced the lung and systemic oxidative stress, suggesting that the effects of 2-APB on vascular remodeling and pulmonary hypertension are independent on the reduction of the oxidative stress. Thus, our results supported that STIM-activated TRPC-ORAI Ca2+ channels contributes to the lung vascular remodeling and pulmonary hypertension induced by CIH.

Assessment of the Systemic Oxidative Stress in Preeclampsia

Abstract Preeclampsia (PE) is a major complication of pregnancy with both mother and fetal adverse outcomes. Pregnancy is a state of increased oxidative stress that has been reported to be exacerbated when complicated with preeclampsia. However, conflicting data are available in literature regarding the systemic oxidative stress in PE pregnancies. The present pilot study was purported to assess systemic oxidative stress in preeclamptic vs healthy pregnancies. To this aim plasma derived compounds of reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) were determined in mild and severe preeclamptic pregnancies using the Diacron equipment. Both healthy and preeclamptic pregnancies showed high levels of systemic oxidative stress. Paradoxically, significantly higher values of d-ROMs were found in healthy pregnancies as compared to the PE ones. At variance, in preeclamptic pregnancies, a major increase in the plasma antioxidant capacity occurred. In this pilot study, we report an increase in the systemic antioxidant capacity in preeclamptic pregnancies.

Regular short exposures to cold environment as an adjunct therapy for patients with sleep apnea syndrome (SAS)

Sleep Apnea Syndrome (SAS) is a sleep related-breathing disorder with several features such as systemic inflammation, oxidative stress, cognitive impairment and a poor sleep quality. Patients with SAS have an increased risk of cardiovascular diseases. There is no real effective treatment that prevents and treats all of these illness symptoms. Cooling therapies are often used in sport medicine and in athletes after training and competitions to reduce inflammation, oxidative stress and to enhance sleep quality. In this short article, we hypothesize that the use of cooling therapies (whole body cryotherapy, cold-water immersion…) could be an efficient strategy to facilitate the treatment of SAS patients by reducing the level of systemic inflammation and oxidative stress and enhancing sleep quality.

Angiotensin II type 1 receptor is involved in flow-induced vasomotor responses of isolated middle cerebral arteries: role of oxidative stress.

This study aimed to determine the mechanosensing role of angiotensin II type 1 receptor (AT1R) in flow-induced dilation (FID) and oxidative stress production in middle cerebral arteries (MCA) of Sprague-Dawley rats. Eleven-week old, healthy male Sprague-Dawley rats on a standard diet were given the AT1R blocker losartan (1 mg/mL) in drinking water (losartan group) or tap water (control group) ad libitum for 7 days. Blockade of AT1R attenuated FID and acetylcholine-induced dilation was compared with control group. Nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) and cyclooxygenase inhibitor indomethacin (Indo) significantly reduced FID in control group. The attenuated FID in losartan group was further reduced by Indo only at Δ100 mmHg, whereas l-NAME had no effect. In losartan group, Tempol (a superoxide scavenger) restored dilatation, whereas Tempol + l-NAME together significantly reduced FID compared with restored dilatation with Tempol alone. Direct fluorescence measurements of NO and reactive oxygen species (ROS) production in MCA, in no-flow conditions revealed significantly reduced vascular NO levels with AT1R blockade compared with control group, whereas in flow condition increased the NO and ROS production in losartan group and had no effect in the control group. In losartan group, Tempol decreased ROS production in both no-flow and flow conditions. AT1R blockade elicited increased serum concentrations of ANG II, 8-iso-PGF2α, and TBARS, and decreased antioxidant enzyme activity (SOD and CAT). These results suggest that in small isolated cerebral arteries: 1) AT1 receptor maintains dilations in physiological conditions; 2) AT1R blockade leads to increased vascular and systemic oxidative stress, which underlies impaired FID.NEW & NOTEWORTHY The AT1R blockade impaired the endothelium-dependent, both flow- and acetylcholine-induced dilations of MCA by decreasing vascular NO production and increasing the level of vascular and systemic oxidative stress, whereas it mildly influenced the vascular wall inflammatory phenotype, but had no effect on the systemic inflammatory response. Our data provide functional and molecular evidence for an important role of AT1 receptor activation in physiological conditions, suggesting that AT1 receptors have multiple biological functions.

The antioxidant effect of triptolide contributes to the therapy in a collagen-induced arthritis rat model

ABSTRACT Background As a chronic autoimmune disease, rheumatoid arthritis (RA) is related to oxidative stress, which may lead to the occurrence and persistence of inflammation in RA. The purpose of this study is to evaluate the potential antioxidant effect of triptolide in collagen-induced arthritis (CIA) rat model. Methods We examined the severity of arthritis, levels of local and systemic oxidative stress, periarticular bone erosion and weight of organs in CIA rats treated with triptolide. Results We found that triptolide decreased the paw thickness and clinical arthritis score, significantly. The mRNA expression and activity of myeloperoxidase and inducible nitric oxide synthase were remarkably decreased in the paws of the CIA rats after triptolide treatment. Triptolide significantly inhibited the levels of nitrite and nitrate in serum, as well as the urinary level of dityrosine. Triptolide treatment also markedly increased bone volume of tibia, but suppressed epiphyseal plate thickness of both femur and tibia. In addition, there was no significant difference in the weight of organs after the therapy, except decreased spleen weight. Conclusions These results suggested that the local and systemic oxidative stress was enhanced in the CIA rats and the therapeutic dose of triptolide had a definite antioxidant effect.

Effects of antihypertensive treatment on systemic inflammation, oxidative stress and proinflammatory cytokine levels

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.

Influence of skin melanisation and ultraviolet radiation on biomarkers of systemic oxidative stress

Skin melanisation ranges widely across human populations. Melanin has antioxidant properties and also acts as a filter to solar ultraviolet radiation (UVR) incident upon the skin. In this study we firstly examined whether melanin level might influence baseline levels of systemic oxidative stress, in 65 humans in vivo from the same geographical area ranging from the lightest to darkest skin type (phototype I-VI). This was examined in winter-time (latitude 53.5°N). Remarkably, we found that urinary biomarkers of oxidatively-generated DNA damage (8-oxodG) and RNA damage (8-oxoGuo) were significantly correlated with skin lightness (L*), such that 14–15% of the variation in their baseline levels could be explained by skin colour. Next we exposed 15 humans at the extremes of skin melanisation to a simulated summer-time exposure of solar UVR (95% UVA, 5% UVB; dose standardised to sunburn threshold), following which they provided a sample of every urine void over the next five days. We found that UVR induced a small but significant increase in urinary 8-oxodG and 8-oxoGuo, with differing kinetics between skin types. Thus greater melanisation is associated with protection against systemic oxidative stress, which may reflect melanin's antioxidant properties, and solar UVR exposure also influences systemic oxidative stress levels in humans. These novel findings may have profound implications for human physiology and health.

Antioxidant supplementation, redox deficiencies and exercise performance: A falsification design

The aim of the present study was to validate the idea of personalized redox supplementation by subjecting individuals to targeted and non-targeted antioxidant supplementation schemes. Seventy-three volunteers were screened for plasma vitamin C and erythrocyte glutathione levels. Three groups were formed: i) the “low vitamin C″ group (12 individuals with the lowest vitamin C levels; Low VitC), ii) the “low glutathione” group (12 individuals with the lowest glutathione levels; Low GSH) and iii) a control group (12 individuals with moderate vitamin C and glutathione levels). The three groups received 1 g of vitamin C or 1.2 g of NAC daily for 30 days in a crossover design with a wash-out period of 30 days. Both antioxidant treatments reduced the increased resting systemic oxidative stress levels, assessed via urine F2-isoprostanes, in the Low VitC and Low GSH groups (P < .05). A significant group × time interaction (P < .05) was found for VO2max and isometric peak torque after both treatments, with the Low VitC and Low GSH groups exhibiting improved performance only after the targeted treatment (vitamin C and NAC, respectively). A significant group × time interaction (P < .05) was found for fatigue index after NAC treatment, but not after vitamin C treatment. No interaction was found for the Wingate test after both treatments. Most of the evidence verifies the idea that antioxidant supplementation increases performance when a particular deficiency is reversed. This indicates that the presence of oxidative stress per se does not rationalize the use of antioxidants and emphasizes the need to identify “responsive” phenotypes.

Features of clinical and laboratory indicators in alcoholic liver disease in combination with arterial hypertension depending on T786C polymorphism of the eNOS gene

The goal of the work. Assess the relationship between eNOS gene genotypes (T786C) and some clinical and laboratory parameters in patients with alcoholic liver disease (ALD) in combination with arterial hypertension (AH).Material and methods. 97 patients diagnosed with AHP were examined: 62 patients with ALD with AH (group A) and 35 patients with ALD (group B). Serum content of C-reactive protein, tumor necrosis factor-α (TNFα), transforming growth factor-β1 (TGFβ1), interleukin-10 (IL-10), 8-isoprostane, D-dimer was determined by enzyme-linked immunosorbent assay. The functional state of the endothelium was assessed by the content in the blood of stable metabolites of nitrogen monoxide (nitrites / nitrates), endothelin-1 (ET-1), intercellular adhesion molecules-1 (ICAM-1). Total blood coagulation potential (plasma recalcification time), prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), plasma fibrinogen levels, antithrombin III (ATIII) activity, factor XIII (F XIII) activity was determined by traditional methods. Spontaneous platelet aggregation was also studied. To determine the eNOS mutation (T786C), rs2070744 used a protocol with oligonucleotide primers using the method of allele-specific PCR.Results. When studying the frequency of genotypes by the polymorphic variant of the eNOS gene (T786C), it was found that the frequency of TT genotype among patients with ALD with hypertension was 46.8%, CT - 57.1% and SS - 17.2%. Among patients with ALD, the following distribution of genotypes was found: TT - 25.7%, ST - 57.1% and SS - 17.2%. We found a significant difference between the group of patients with ALD with AH and the isolated group of ALD by TT genotype. It was found that the level of ET-1 and the intercellular adhesion molecule (ICAM-1) were significantly higher in patients with ALD with AH by TT genotype compared with the isolated course of ALD. However, the level of total nitric oxide in the combined course of ALD with hypertension was lower than in patients with ALD without hypertension in the presence of this genotype. At the same time, in the combined course of ALD and hypertension, the level of systemic inflammation and oxidative stress is associated with the TT genotype by a polymorphic variant of the eNOS gene (T786C). When studying the state of hemostasis in the combined course of ALD and hypertension, it was found that APTT for the TT genotype was 17.7% higher than in group B. This indicator also had a difference in the middle group between the TT and CT genotypes (by 13.1%) and TT and CC (by 28.3%). The level of D-dimer between groups A and B also had a significant difference in the TT genotype (higher by 14.7% for the combination of ALD and AH). Spontaneous platelet aggregation was significantly higher by 7.7% in patients with ALD with hypertension by TT genotype. In the latter group of patients, factor XIII was significantly lower by 12.6% compared with the group of patients with ALD. Indicators such as plasma recalcification time, prothrombin index and time, thrombin time did not differ significantly between groups of patients.Conclusion. The development of hypertension in patients with ALD is associated with the presence of a homozygous TT genotype for a polymorphic variant of the eNOS gene (T786C). It was found that in patients with ALD with hypertension by TT genotype higher levels of ET-1 and intercellular adhesion molecules ICAM-1 are observed at a lower level of total nitric oxide compared with patients with ALD. The most probable differences in systemic inflammation (IL-10, CRP, TGFβ1) and oxidative stress marker (8-isoprostane) are characteristic of the TT genotype for the polymorphic variant of the eNOS gene (T786C) in patients with ACP with hypertension compared with the isolated course of ALD. Hemostasis parameters such as APTT, antithrombin III, D-dimer, spontaneous platelet aggregation and factor XIII were associated with the TT genotype in patients with ALD with hypertension by the polymorphic variant of the eNOS gene (T786C).

Gamma-glutamyltransferase, arterial remodeling and prehypertension in a healthy population at low cardiometabolic risk.

Plasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy subjects at low cardiometabolic risk, the associations of plasma GGT with carotid artery intima-media thickness (IMT), luminal diameter and prehypertension; in 154 subjects was evaluated also the association with aortic stiffness (cfPWV). Associations were controlled for insulin sensitivity, C-reactive protein, and life-style habits. In the main population, BP was remeasured after 3 years. Carotid diameter and cfPWV, but not IMT, were directly and independently related to plasma GGT. Subjects with prehypertension (N = 330) had higher GGT as compared with subjects with normal BP (22 [14] vs 17 [11] IU/L; adjusted P = 0.001), and within prehypertensive subjects, those who developed hypertension during 3 years had higher GGT than those without incident hypertension (27 [16] vs 21 [14] IU/L; adjusted P < 0.05). Within subjects with arterial stiffness measurement, those with prehypertension (N = 79) had higher both GGT and arterial stiffness (25 [14] vs 16 [20] IU/L and 9.11 ± 1.24 vs 7.90 ± 0.94 m/s; adjusted P < 0.01 and <0.05). In the view of previous evidence linking plasma GGT concentration to the level of systemic oxidative stress, our findings suggest a role of oxidative stress in subclinical arterial damage and in prehypertension, even in healthy subjects free of cardiometabolic risk. Arterial organ damage may represent the link between GGT and hypertension.

Rapid decreases of key antioxidant molecules in critically ill patients: A personalized approach

Oxidative stress is regarded a key component of critical illness and has been associated with poor prognosis in Intensive Care Unit (ICU) patients. Diverse antioxidant treatments have been applied to combat oxidative stress in ICU, yet the results were typically disappointing. An explanation for this failure is that all studies utilized antioxidants indiscriminately and did not take into account the antioxidant profile of the patients. The aim of the present study was to investigate whether critically ill patients experience different insufficiencies in three major antioxidants with a "recycling" redox relationship (vitamin C, vitamin E and glutathione) and in the central reductant molecule of many enzymatic antioxidants (NADPH). Sixty mechanically-ventilated adult medical critically ill patients (age: 63.5±17.1; APACHE II score: 21.2±7.4; Glasgow Coma Scale: 6.2±1.9) were enrolled in the study, while 20 healthy age-matched volunteers served as control group. The antioxidant profile and the level of systemic oxidative stress (F2-isoprostanes) were measured at ICU admission and at days 1 and 7. The majority of the ICU patients developed rapid and severe antioxidant insufficiencies (by exhibiting less than 50% of the control values) in one (22/60), two (7/60) or three (2/60) of the antioxidants measured, despite the almost similar levels of oxidative stress. The wide heterogeneity in antioxidant decreases in response to ICU stay highlights the importance of patient stratification when planning to apply antioxidant treatments and indicates that the successful delivery of personalized clinical nutrition may depend on our ability to identify "responsive" phenotypes.

The investigation of the relationships of demodex density with inflammatory response and oxidative stress in rosacea

The relationships of demodex density with systemic oxidative stress, inflammatory response, and clinical severity in rosacea are not clear. This study aimed to (a) analyze the levels of systemic oxidative stress, antioxidant capacity, inflammatory parameters, and matrix metalloproteinases (MMPs) in systemic circulation in patients with rosacea, (b) identify the relationship between mite density and both oxidative stress and inflammation, and (c) investigate the role of photoaging and sebum secretion in etiopathogenesis. Forty patients with rosacea and 40 age-, sex-, and skin phenotype-matched healthy volunteers were included in the study. Clinical disease severity of the patients was determined. Sebum levels were measured in both the groups, and photoaging was evaluated. Reflectance confocal microscopy was used to calculate demodex density. Serum total antioxidant capacity (TAC), total oxidant capacity (TOC), myeloperoxidase (MPO), MMP-1, MMP-9, arylesterase (ARES), interleukin-1β (IL-1β), paraoxonase-1 (PON-1), and tumor necrosis factor-α (TNF-α) levels were also analyzed. The patients with rosacea had significantly higher serum TOC and lower TAC levels (p < 0.001). The serum ARES and PON-1 levels were significantly lower (p = 0.045 and p < 0.001, respectively); however, the serum levels of MMP-1, MMP-9, IL-1β and MPO were higher in the patient group. Demodex parameters were higher in the patient group compared to the control group. There was no significant correlation between the number of mites and disease severity. In addition, the number of mites was not correlated with the serum levels of TAC, TOC, OSI, MPO, MMP-1, MMP-9, ARES, PON-1, TNF-α, and IL-1β. However, sebum levels were directly proportional to the number of mites. Photoaging severity was similar between the patients and control subjects. The changing sebaceous microenvironment in rosacea leads to an increase in the number of demodex mites. However, increased demodex density does not alter disease severity, level of oxidative stress, or inflammation. Although none of the patients with rosacea had any underlying systemic disease, patients' systemic oxidative stress and inflammation parameters were found high in systemic circulation. It is assumed that the patients with rosacea are more prone to systemic diseases.