Systemic Oxidative Stress Markers Research Articles

Effects of smoking on local and systemic oxidative stress markers in individuals with periodontitis

Aim: This study aimed to assess the effects of smoking on systemic and local oxidative stress markers in patients with periodontitis. Methods: A total of 72 patients with periodontitis [38 smokers (S +P+), 34 non-smokers (S-P+)] and 54 periodontally healthy individuals [28 smokers (S+P-), 26 non-smokers (S-P-, control)] were included. After clinical measurements and samplings, the cotinine level, total antioxidant capacity (TAOC), total oxidative status (TOS), and malondialdehyde (MDA) level in the serum and saliva were determined, and the oxidative stress index (OSI) was calculated. Kruskal-Wallis and Mann-Whitney U tests were used for multiple and pairwise comparisons. Correlations were analyzed using Pearson correlation coefficient. P<0.05 was considered statistically significant. Results: Smoking and periodontitis decreased the serum and salivary TAOCs and increased the TOS, MDA level, and OSI. The smokers with periodontitis had the lowest TAOC and the highest TOS, MDA level, and OSI, while the controls had the highest TAOC and the lowest TOS, MDA level, and OSI. The systemic and local effects of smoking seemed more pronounced than those of periodontitis in the oxidative stress study, but no significant difference was identified between the smoking (S+P-) and periodontitis (S-P+) groups. The clinical parameters and oxidative stress markers showed both substantial positive and negative relationships in all groups (p<0.01). Conclusions: It can be concluded that smoking and periodontitis (S+P+) are associated with a decrease in serum and salivary TAOCs and an increase in TOS, MDA levels, and OSI. Smoking has a similar effect as periodontitis on local and systemic oxidative stress, and oxidative stress caused by smoking may be a significant factor in the pathophysiology of periodontitis.

The Effect of High-Salt Diet on Oxidative Stress Production and Vascular Function in Tff3−/−/C57BL/6N Knockout and Wild Type (C57BL/6N) Mice

Introduction: It is well documented that high-salt (HS) diet increases systemic and vascular oxidative stress in various animal models and in humans, leading to impairment of vascular reactivity. The present study examined the interaction of genotype and HS diet intake and the potential effects of oxidative stress – antioxidative system balance on the flow-induced dilation (FID) in pressurized carotid arteries of normotensive Tff3−/−/C57BL/6N knockout mice and their wild-type (WT) controls. Methods: Male, ten-week-old transgenic Tff3−/−/C57BL/6N (Tff3−/−) knockout mice and WT/C57BL/6N (WT) (parental strain) healthy mice were divided in LS (0.4% NaCl in rodent chow) and HS (4% NaCl in rodent chow fed for 1 week) groups. Additionally, LS and HS groups were treated with 1 mmol/L 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) dissolved in the drinking water. After anesthesia with ketamine chloride (100 mg/kg) and midazolam (5 mg/kg), blood pressure was measured, carotid arteries and aortas were isolated, and blood samples were collected. Results: FID was decreased in WT_HS mice and restored by superoxide scavenger TEMPOL in vivo. On the other hand, attenuated FID of Tff3−/− mice was not further affected by HS diet or TEMPOL in vivo treatment. Vascular superoxide/reactive oxygen species levels were increased with HS diet in both strains and restored by TEMPOL. HS upregulated glutathione peroxidase 1 (GPx1) gene expression in WT_HS and Tff3−/−_HS mice, while GPx activity was significantly decreased only in WT_HS group. Systemic (serum) markers of oxidative stress (oxLDL and AOPP) and arterial blood pressure were similar among groups. Conclusion: HS diet increases vascular oxidative stress and impairs vasodilation in WT mice. Tff3 gene deficiency attenuates vasodilation per se, without further effects of HS intake. This can be attributed to vascular upregulation of antioxidative enzyme GPx1 in Tff3−/−/C57BL/6N mice conferring protection from oxidative stress.

High-intensity interval training mitigates the progression of periodontitis and improves behavioural aspects in rats.

To investigate the effects of high-intensity interval training (HIIT) on periodontitis (PD) progression and behavioural outcomes. Forty-eight Wistar rats were divided into four groups: non-trained (NT); non-trained with PD; HIIT with PD; and HIIT. The HIIT protocol, involving daily treadmill sessions, spanned 8 weeks, with PD induced by ligature after the 6th week. Behavioural tests were conducted to assess anxiety and memory. Post euthanasia, we evaluated the systemic inflammatory profile and oxidative stress markers in the hippocampus and amygdala. A morphological evaluation and elemental composition analysis of the mandibular alveolar bone were performed. PD exacerbated alveolar bone level, bone surface damage and alterations in calcium and phosphorus percentages on the bone surface (p < .05), while HIIT attenuated these changes (p < .05). HIIT improved systemic inflammatory markers altered by PD (tumour necrosis factor [TNF]-α, interleukin [IL]-10, TNF-α/IL-10 and IL-1β/IL-10 ratios, p < .05). PD animals exhibited lower total antioxidant capacity and levels of thiobarbituric acid reactive substances in the amygdala and hippocampus, respectively (p < .05). HIIT maintained these parameters at levels similar to those in NT animals. HIIT improved anxiety and memory outcomes altered by PD (p < .05). HIIT attenuates systemic inflammation, anxiety and memory outcomes promoted by PD.

The Effects Of Surgical Arthroscopy And Intraarticular Medication On The Antioxidant System And Lipid Peroxidation In Knee Osteoarthritis

&lt;b&gt;Aim: &lt;/b&gt;This study aims to evaluate the effects of joint surgery through arthroscopy, intraarticular medication, and antioxidant therapy on the antioxidant system and lipid peroxidation in patients with knee osteoarthritis (KOA). The study examines the ability of high-molecular weight hyaluronan, sodium hyaluronate, and oral Vitamin E to modulate oxidative stress markers in the knee joint.&lt;br /&gt; &lt;b&gt;Methods and Materials: &lt;/b&gt;There were 60 patients diagnosed with KOA that were divided into four groups according to the type of treatment for this prospective study at the Department of Orthopaedics and Traumatology. Blood and synovial fluid samples collected before and after treatment were evaluated for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), lipid peroxidation (malondialdehyde, MDA) catalase (CAT). SPSS software was used to perform statistical analysis where the significance level was set at p&amp;lt;0.05.&lt;br /&gt; &lt;b&gt;Results: &lt;/b&gt;Synovial fluid malondialdehyde levels that showed a decreased tendency among treated groups indicated a reduced state of antioxidant activity. However, no significant changes were observed in systemic oxidative stress markers. These findings show that localized antioxidant therapy within the knee can be effective in reducing oxidative stress, therefore, may have implications for nonsurgical treatment of KOA.&lt;br /&gt; &lt;b&gt;Conclusion: &lt;/b&gt;The results emphasize possible gains made from combining surgical arthroscopy together with antioxidant treatment in managing KOA. By reducing the level of oxidative stress within the knee joint, this combined method can provide a viable solution to improve symptoms and quality of life among KOA patients.

Human In Vitro Oxidized Low-Density Lipoprotein (oxLDL) Increases Urinary Albumin Excretion in Rats.

Hypercholesterolemia-associated oxidative stress increases the formation of oxidized low-density lipoprotein (oxLDL), which can affect endothelial cell function and potentially contribute to renal dysfunction, as reflected by changes in urinary protein excretion. This study aimed to investigate the impact of exogenous oxLDL on urinary excretion of albumin and nephrin. LDL was isolated from a patient with familial hypercholesterolemia (FH) undergoing lipoprotein apheresis (LA) and was oxidized in vitro with Cu (II) ions. Biochemical markers of LDL oxidation, such as TBARS, conjugated dienes, and free ε-amino groups, were measured. Wistar rats were treated with a single intraperitoneal injection of PBS, LDL, or oxLDL (4 mg of protein/kg b.w.). Urine was collected one day before and two days after the injection. We measured blood lipid profiles, urinary protein excretion (specifically albumin and nephrin), and markers of systemic oxidative stress (8-OHdG and 8-iso-PGF2α). The results showed that injection of oxLDL increased urinary albumin excretion by approximately 28% (310 ± 27 μg/24 h vs. 396 ± 26 μg/24 h, p = 0.0003) but had no effect on nephrin excretion. Neither PBS nor LDL had any effect on urinary albumin or nephrin excretion. Additionally, oxLDL did not affect systemic oxidative stress. In conclusion, hypercholesterolemia may adversely affect renal function through oxidatively modified LDL, which interferes with the renal handling of albumin and leads to the development of albuminuria.

An Evaluation of the Hematological Markers of Systemic Inflammation and Oxidative Stress in Vitiligo: A Case-Control Study.

Introduction Melanocyte dysfunction in vitiligo is considered to be due to genetics, inflammation, and autoimmunity. Research has shown that oxidative stress plays a significant role in triggering these conditions. Currently, there are several markers indicating hematological inflammation and oxidative stress. This study aimed to investigate the status of inflammation and oxidative stress markers in vitiligo. Methods This study included patients with vitiligo and age-gender-matched healthy controls.C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-high-density lipoprotein ratio (MHR) and extent of vitiligo were calculated and compared. Results The study included 138 participants (69 vitiligo and 69 controls). The mean was 41.46 years with a female predominance (55.1%). The patient group demonstrated higher levels of platelets, neutrophils, CRP, NLR, MLR, PLR, and HDL and lower levels of lymphocytes and HDL compared to the control group (p>0,05).The only significantly different value between the groups was MHR (p=0.03). The generalized vitiligo group demonstrated higher levels of platelets, neutrophils, monocytes, CRP, NLR, PLR, and MLR, and lower levels of lymphocytes and HDL compared to the localized group. The only significantly different values between the groups were MHR and MLR (p=0.02, p=0.03). Conclusion This study found that MHR and CRP values were higher in vitiligo patients. Additionally, MHR and MLR values were higher in patients with generalized vitiligo. These results suggest that MHR is a reliable indicator marker for systemic inflammation and oxidative stress in vitiligo.

Gallic Acid Protects from Sepsis-Induced Acute Lung Injury.

Sepsis, a leading global cause of morbidity and mortality, involves multiple organ dysfunction syndromes driven by free radical-mediated processes. Uncontrolled inflammation in early sepsis stages can lead to acute lung injury (ALI). Activated leukocytes generate reactive oxygen species, contributing to sepsis development. Gallic acid, a phenolic compound, is known for its antimicrobial properties. This study aims to observe gallic acid's protective and restorative effect on the lungs in an experimental sepsis model. Male Wistar albino rats were subjected to a feces intraperitoneal injection procedure (FIP) to induce sepsis. Four groups were formed: normal control, FIP alone, FIP with saline, and FIP with gallic acid. Gallic acid was administered intraperitoneally at 20 mg/kg/day. Blood samples were collected for biochemical analysis, and computed tomography assessed lung tissue histopathologically and radiologically. Gallic acid significantly decreased malondialdehyde, IL-6, IL-1β, TNF-α, CRP levels, oxidative stress, and inflammation indicators. Lactic acid levels decreased, suggesting improved tissue oxygenation. Histopathological examinations revealed reduced lung damage in the gallic-acid-treated group. Computed tomography confirmed lower lung density, indicating less severe inflammation. Arterial blood gas analysis demonstrated improved oxygenation in gallic-acid-treated rats. Gallic acid exhibited anti-inflammatory and antioxidant effects, reducing markers of systemic inflammation and oxidative stress. The findings support its potential to protect against ALI during sepsis. Comparable studies underline gallic acid's anti-inflammatory properties in different tissues. Early administration of gallic acid in sepsis models demonstrated protective effects against ALI, emphasizing its potential as an adjunct therapy to mitigate adverse outcomes. The study proposes gallic acid to reduce mortality rates and decrease the need for mechanical ventilation during sepsis-induced ALI.

Crusted scabies in a rabbit model: a severe skin disease or more?

BackgroundAround 200–300 million people are estimated to be affected by scabies annually worldwide. However, the mechanisms by which this disease may affect the general condition of the host are not entirely clear. The aim of the present study was to evaluate the systemic changes that may accompany crusted scabies in both treated and non-treated experimental animals.MethodsMale New Zealand rabbits were infected with Sarcoptes scabiei var. cuniculi and divided into the following three groups: control, ivermectin-treated, and fluralaner-treated. Several methods were used to evaluate the systemic changes, including histopathological examination of the liver, kidney, heart, and spleen, as well as the measurement of serum biochemical parameters and immunological parameters.ResultsSeveral definite structural and functional changes at the systemic level were revealed, as evidenced by the observed histopathological changes in the tissue sections of internal organs and the highly significant increases in markers of systemic inflammation, serum procalcitonin, and oxidative stress markers. Abnormalities in the liver and renal function results, as well as in the serum lipid profile, were also noted. Additionally, a disorganized immune response was noted, evidenced by a mixed type 1 and type 2 helper T cell response. Although there was notable clinical and parasitological cure in the ivermectin-treated group, the histopathological, biochemical, and immunological markers indicated incomplete resolution. In contrast, the fluralaner-treated group exhibited a nearly complete resolution of changes in these parameters.ConclusionsWe conclude that crusted scabies is a systemic syndrome that can affect several organs besides the skin. Inflammation, oxidative stress, and possibly bacterial infections, are all implicated as underlying mechanisms of tissue damage due to the disease. We recommend that fluralaner, a promising scabicidal agent, should be studied for possible human use, and especially for control programs.Graphical

Finasteride effectively attenuates the impairments of left ventricular function and cardiac sympathovagal balance in both aging and obese male rats via reducing systemic oxidative stress

Abstract Background Cardiovascular diseases are commonly found in the elderly and obese population manifested by left ventricular (LV) dysfunction and impaired cardiac sympathovagal balance. Finasteride (FIN), a 5-alpha reductase inhibitor (5-ARI), is a universal prescription for patients with benign prostatic hyperplasia (BPH). Since BPH is commonly found in obesity and aging, it is essential to investigate whether FIN could have an impact on the LV function and cardiac sympathovagal balance in either elderly or obese conditions. Purpose We tested the hypothesis that impaired LV function and cardiac sympathovagal balance are observed in aging and obese conditions, and FIN improves these parameters through a reduction of systemic oxidative stress in both aging and obese male rats. Methods Twenty-four male Wistar rats (aged 8 weeks old) were randomly divided into 3 groups (n=8/group) to receive one of the followings: 1) normal diet (ND) feeding, 2) ND feeding with D-galactose injection (150 mg/kg/day, subcutaneous injection, 18 weeks) for creating an aging model, and 3) HFD feeding for 18 weeks for creating an obesity model. At week 13, rats in each group were divided into 2 subgroups (n=4/subgroup) and received either a vehicle (drinking water) or FIN (5 mg/kg/day) via oral gavage. At the end of treatment, echocardiography was performed to assess LV function, and the heart rate variability (HRV) was determined to quantify cardiac sympathovagal balance. The blood was collected, and serum was used to determine serum malondialdehyde (MDA) levels as a marker of systemic oxidative stress. Results At week 13, D-galactose injection successfully induced aging as indicated by increasing cardiac p53 protein expression. HFD also caused obesity in those rats as indicated by increased body weight and visceral fat weight. LV dysfunction (as indicated by reduced %LVEF and %LVFS) and cardiac sympathovalgal imbalance (as indicated by an increased LF/HF ratio) were observed in both models (Figure 1A-C). This functional impairment was associated with an increased MDA levels (Figure 1D). Treatment with FIN successfully reduced cardiac sympathovagal imbalance in both models (Figure 1C); however, an improvement of LV function was found only in aging rats-treated with FIN (Figure 1A, B). Consistent with a reduction of cardiac sympathovagal imbalance, FIN decreased systemic oxidative stress in both models (Figure 1D). Conclusions FIN effectively improved cardiac sympathovagal balance in rats under both aging and obese conditions. However, FIN reduced LV dysfunction only in aging rats. Interestingly, FIN did not affect these cardiac parameters in normal healthy rats. These findings suggest the cardioprotective potential of FIN in both aging and obese populations.

Systemic inflammation and oxidative stress markers in patients with unipolar and bipolar depression: A large-scale study

ObjectiveNumerous studies have demonstrated that neutrophil/HDL ratio (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL (MHR) ratio, platelet/HDL ratio (PHR), neutrophil/ALB ratio (NAR) and platelet/ALB ratio (PAR) can serve as systemic inflammation and oxidative stress markers in a variety of diseases. However, few studies have estimated the associations of these markers with unipolar depression (UD) and bipolar depression (BD), as well as psychotic symptoms in UD and BD. Methods6297 UD patients, 1828 BD patients and 7630 healthy subjects were recruited. The differences in these indicators among different groups were compared, and the influencing factors for the occurrence of UD or BD and psychotic symptoms were analyzed. ResultsThese ratios displayed unique variation patterns across different diagnostic groups. BD group exhibited higher NHR, LHR, MHR, NAR and lower PAR than UD and HC groups, UD group showed higher MHR than HC group. The psychotic UD group had higher NHR, LHR, MHR and NAR than non-psychotic UD group. Higher LHR, MHR, NAR and lower PAR were risk factors in BD when compared to UD group. ConclusionsOur study demonstrated differences in inflammation and oxidative stress profile between UD and BD patients, as well as between subjects with or without psychotic symptom exist, highlighting the role of inflammation and oxidative stress in the pathophysiology of UD and BD.

148 Evaluation of Multicarbohydrase Supplementation in Soluble and Insoluble Fiber-Based sow Diets on Markers of Immune Function, Inflammation, and Oxidative Status at mid and Late Gestation

Abstract Carbohydrase supplementation in soluble and insoluble fiber-based diets can improve the health, gastrointestinal function, and livability of growing pigs. However, its efficacy in sow diets is incompletely understood. The experimental objective was to investigate the effects of soluble (20% sugar beet pulp) versus insoluble (20% reduce oil corn DDGS) dietary fiber with or without multicarbohydrase supplementation on systemic markers of gut barrier integrity, inflammation, and oxidative stress of sows at mid and late gestation. On d 28 of gestation, 36 confirmed gestating sows (186 ± 4.6 kg BW) were blocked by parity and randomly assigned to 1 of 4 diets (n = 8) in a 2×2 factorial arrangement. Factors included fiber type of either insoluble fiber (IF; 16.91 IDF%) or soluble fiber (SF; 5.26 SDF%) and with (+) or without (-) enzyme supplementation (0.05%, Rovabio Advance P10; Adisseo, Antony, France). Diets were fed from d 28 to d 109 of gestation at a feeding level of 2.4 kg/d. On d 50 and d 99 of gestation, before an 8-d metabolism collection period, serum and plasma were collected via jugular venipuncture and analyzed for malondialdehyde, total antioxidant capacity (TAC), lipopolysaccharide binding protein (LBP), and a 13-plex cytokine array. Data were analyzed as repeated records using a linear mixed model (PROC Mixed, SAS 9.4) with block as a random effect, and fiber type, enzyme supplementation, and collection period and their interaction as fixed effects. Relative to mid gestation, serum malondialdehyde concentrations were greater in late gestation (5.53 vs. 7.52 μmol/mL; Period P = 0.015), and a similar effect was observed for plasma TAC (5.81 vs. 6.59 mmol/L; Period P = 0.008). Sows fed SF tended to have increased circulating Interleukin (IL)-10 (4.97 vs. 8.59 ng/mL; Fiber P = 0.096) and had increased serum IL-6 (0.65 vs. 1.40 ng/mL; Fiber P = 0.032). Multicarbohydrase supplementation decreased serum IL-4 (17.97 vs. 9.67 ng/mL; Enzyme P = 0.012). Irrespective of collection period, multicarbohydrase supplementation increased Granulocyte-Macrophage Colony-stimulating factor in sows fed IF but reduced it in those fed SF (220, 430, 550, 260 pg/mL for IF-, IF+, SF-, and SF+, respectively; Fiber×Enzyme P = 0.042). Sows fed SF+ had increased serum IL-1 receptor antagonist (2.12, 2.20, 2.69, 4.18 ng/ml for IF-, IF+, SF-, and SF+, respectively; Fiber×Enzyme P = 0.035), and IL-2 (1.53, 1.67, 1.64, 2.89 ng/mL for IF-, IF+, SF-, and SF+; Fiber×Enzyme P = 0.042). In the presence of IF, multicarbohydrases increased serum LBP, but not when supplemented with SF (9.68, 10.90, 10.02, 9.68 ng/mL for IF-, IF+, SF-, and SF+, respectively; Fiber×Enzyme P = 0.028). Circulating IL-8 (0.24 vs. 0.10 ng/mL) and Tumor Necrosis Factor-a (1.26 vs. 0.60 ng/ml) were reduced in sows fed multicarbohydrases (Enzyme P &amp;lt; 0.05). Collectively, supplementing multicarbohydrases may reduce systemic endotoxin and inflammatory pressures throughout gestation, but mechanisms are unique to dietary fiber type.

Evaluation of Ocular and Systemic Oxidative Stress Markers in Ocular Rosacea Patients.

To investigate oxidative stress markers in tears and serum of patients with ocular rosacea and to examine their association with both ocular surface parameters and cutaneous rosacea subtypes. This prospective study includes rosacea patients with ocular involvement and healthy controls. We performed ophthalmological examination of all participants and collected tear breakup time (TBUT), Schirmer, Meibomian gland dysfunction (MGD) and Ocular Surface Disease Index (OSDI) scores. We quantified the total antioxidant status (TAS), total oxidant status (TOS), and arylesterase (ARE) levels from tear and serum samples, and calculated the oxidative stress index (OSI). We also classified patients into phymatous, erythematotelangiectatic, papulopustular subtypes. We included 90 ocular rosacea patients and 30 healthy controls. Oxidative stress (TOS, OSI) levels were significantly higher (P < 0.01) and antioxidant levels (TAS, ARE) were significantly lower (P < 0.01) in both tear and serum samples of ocular rosacea patients as compared to controls. We found a significant positive correlation between the tear and serum values regarding oxidative stress parameters (P < 0.05). Besides, OSI was negatively correlated with TBUT and positively correlated with MGD score (meiboscore) and OSDI (P < 0.05). The Schirmer score was not correlated with OSI. No difference was found between the cutaneous subtypes with respect to TAS, TOS, ARE, and OSI results. In this study, we identified oxidative stress markers in the serum and tears of ocular rosacea patients and showed their correlation with clinical signs of MGD, suggesting that oxidative stress contributes to ocular rosacea pathogenesis and that oxidative stress could be an indicator of MGD severity.

Dynamics of oxidative stress and immune responses in neonatal calves during diarrhea

Oxidative stress is the imbalanced redox status between oxidant production and their scavengers leading to intestinal physiological dysfunction. However, the role of systemic and local oxidative status during neonatal calf diarrhea is not known. This study assessed systemic (serum) and local (fecal) oxidative status when calves either naturally developed diarrhea or naturally recovered. Healthy calves were enrolled in the study at d 18 of age, and their health status was monitored from the enrollment. Based on their enteric health status on d 21 and 28, calves were grouped as continuous diarrhea from d 21 to 28 (n = 14), diarrhea at d 21 but recovered at d 28 (DH group, n = 19), healthy at d 21 but developed diarrhea at d 28 (HD group, n = 15), and healthy throughout the study (HH group, n = 16). Serum and fecal samples were collected at d 21 and 28 from all calves in the morning 2 h after feeding. Dynamics of oxidative stress indicators including reactive oxygen species (ROS), malondialdehyde (MDA), H2O2, 8-hydroxy-2'-deoxyguanosine (8-OHDG), glutathione peroxidase, superoxide dismutase, catalase (CAT), and total antioxidant capacity and inflammatory indicators TNF-α, IL-1β, IL-4, IL-6, IL-10, and IFN-γ were evaluated using serum samples. In addition, fecal oxidative stress indicators ROS and MDA were measured. Serum ROS, MDA, 8-OHDG, as well as fecal ROS and MDA, were higher, whereas serum CAT and H2O2 were lower in diarrheic calves than those of healthy calves. Serum ROS, MDA, and 8OHDG and fecal ROS and MDA increased in the HD group from d 21 to 28 as they developed diarrhea. In contrast, all these oxidative stress markers decreased in the DH group from d 21 to 28 as they recovered. However, serum H2O2 had an opposite changing trend, which became lower in the HD group and higher in the DH group at d 28. In conclusion, both systemic and local oxidative stress markers and cytokine profiles altered as calves moved from being healthy to having diarrhea or vice versa. Serum ROS, MDA, and 8-OHDG can be used to develop biomarkers to screen calves prone to enteric infections during the preweaning period.

Systemic oxidative stress associates with disease severity and outcome in patients with new-onset or worsening heart failure

BackgroundOxidative stress may be a key pathophysiological mediator in the development and progression of heart failure (HF). The role of serum-free thiol concentrations, as a marker of systemic oxidative stress, in HF remains largely unknown.ObjectiveThe purpose of this study was to investigate associations between serum-free thiol concentrations and disease severity and clinical outcome in patients with new-onset or worsening HF.MethodsSerum-free thiol concentrations were determined by colorimetric detection in 3802 patients from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF). Associations between free thiol concentrations and clinical characteristics and outcomes, including all-cause mortality, cardiovascular mortality, and a composite of HF hospitalization and all-cause mortality during a 2-years follow-up, were reported.ResultsLower serum-free thiol concentrations were associated with more advanced HF, as indicated by worse NYHA class, higher plasma NT-proBNP (P < 0.001 for both) and with higher rates of all-cause mortality (hazard ratio (HR) per standard deviation (SD) decrease in free thiols: 1.253, 95% confidence interval (CI): 1.171–1.341, P < 0.001), cardiovascular mortality (HR per SD: 1.182, 95% CI: 1.086–1.288, P < 0.001), and the composite outcome (HR per SD: 1.058, 95% CI: 1.001–1.118, P = 0.046).ConclusionsIn patients with new-onset or worsening HF, a lower serum-free thiol concentration, indicative of higher oxidative stress, is associated with increased HF severity and poorer prognosis. Our results do not prove causality, but our findings may be used as rationale for future (mechanistic) studies on serum-free thiol modulation in heart failure.Graphical abstractAssociations of serum-free thiol concentrations with heart failure severity and outcomes

Sex differences in the association between systemic oxidative stress status and optic nerve head blood flow in normal-tension glaucoma.

To investigate the association of systemic oxidative stress markers and optic nerve head (ONH) blood flow in normal-tension glaucoma (NTG) patients, as well as sex differences in this association. This was a cross-sectional study of 235 eyes with NTG of 134 patients (56 male, 78 female; mean age, 60.9±14.1 years). Laser speckle flowgraphy (LSFG) was used to measure ONH blood flow (mean blur rate in the tissue area of the ONH; MBR-T) and LSFG pulse-waveform parameters, including flow acceleration index in the tissue area of the ONH (FAI-T). Oxidative stress markers, diacron-reactive oxygen metabolites (d-ROMs), and biological antioxidant potential (BAP) were measured with a free radical elective evaluator. Spearman's rank correlation test and a multivariate linear mixed-effect model were used to investigate factors associated with ONH blood flow. MBR-T was significantly correlated with age (rs = -0.28, p < 0.001), mean arterial pressure (rs = -0.20, p = 0.002), intraocular pressure (rs = 0.24, p < 0.001), peripapillary retinal nerve fiber layer thickness (rs = 0.62, p < 0.001), and disc area (rs = -0.26, p < 0.001), but not with serum d-ROM level. Separate analyses of the subjects divided by sex showed that BAP was positively correlated to MBR-T (rs = 0.21, p = 0.036) and FAI-T (rs = 0.36, p < 0.001) only in male subjects. Similarly, BAP was significantly associated with MBR-T (β = 0.25, p = 0.026) and FAI-T (β = 0.37, p < 0.001) in male subjects in a multivariate linear mixed-effect model. A lower serum antioxidant level, as indicated by BAP, was associated with reduced ONH blood flow only in male NTG patients. Our findings suggest that there are sex differences in the involvement of oxidative stress in the pathogenesis of reduced ocular blood flow in NTG.

Insulin-like growth factor 1 reduces coronary atherosclerosis in pigs with familial hypercholesterolemia.

Although murine models of coronary atherosclerotic disease have been used extensively to determine mechanisms, limited new therapeutic options have emerged. Pigs with familial hypercholesterolemia (FH pigs) develop complex coronary atheromas that are almost identical to human lesions. We reported previously that insulin-like growth factor 1 (IGF-1) reduced aortic atherosclerosis and promoted features of stable plaque in a murine model. We administered human recombinant IGF-1 or saline (control) in atherosclerotic FH pigs for 6 months. IGF-1 decreased relative coronary atheroma in vivo (intravascular ultrasound) and reduced lesion cross-sectional area (postmortem histology). IGF-1 increased plaque's fibrous cap thickness, and reduced necrotic core, macrophage content, and cell apoptosis, consistent with promotion of a stable plaque phenotype. IGF-1 reduced circulating triglycerides, markers of systemic oxidative stress, and CXCL12 chemokine levels. We used spatial transcriptomics (ST) to identify global transcriptome changes in advanced plaque compartments and to obtain mechanistic insights into IGF-1 effects. ST analysis showed that IGF-1 suppressed FOS/FOSB factors and gene expression of MMP9 and CXCL14 in plaque macrophages, suggesting possible involvement of these molecules in IGF-1's effect on atherosclerosis. Thus, IGF-1 reduced coronary plaque burden and promoted features of stable plaque in a pig model, providing support for consideration of clinical trials.

Obesity as a modifying factor of periodontal therapy outcomes: local and systemic adipocytokines and oxidative stress markers.

Adipocytokines and oxidative stress (OS) are involved in the pathogenesis of both obesity and periodontitis. The aim of this study was to evaluate periodontal therapy outcomes in terms of serum and gingival crevicular fluid (GCF) levels of adipocytokines and OS markers in obese patients with periodontitis, in order to have an insight into the association between obesity and periodontitis. A total of 39 patients (20 obese, 19 non-obese) with periodontitis were included in this study. Clinical periodontal parameters were assessed; serum and GCF levels of adipocytokines and OS markers were evaluated by ELISA at baseline and 3months after non-surgical periodontal therapy. Significant improvements in clinical periodontal parameters were observed in both groups at 3months (p < 0.01). While serum levels of TNF-α, leptin, and total oxidant status (TOS) in the obese group were higher at baseline (p < 0.01), leptin levels remained higher at 3months despite a significant decrease (p < 0.01). Although NSPT improved GCF levels of total antioxidant status (TAS) and TOS in both groups, they were significantly different between the groups after therapy (p < 0.05). It seems that leptin, TNF-α, and TOS contribute to systemic inflammatory and oxidative state in patients with obesity. Despite improvements in clinical periodontal parameters, obesity might be a modulating factor in the development and progression of periodontal disease in terms of some adipocytokines and OS markers. Since the global burden of both obesity and periodontitis is continuously increasing, the management of these inflammatory diseases has become more important. The current study contributes to our understanding of the role of OS and adipocytokines on the relationship between obesity and periodontitis by response to periodontal treatment.

Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundUrinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis. MethodsUrinary levels of 8-isoprostane and 2,3-dinor-8-F2-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors. ResultsIn adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F2-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline. ConclusionsHigher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD. Trial registrationThe MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.

N-Acetylcysteine and Postoperative Atrial Fibrillation: Comment.

We read the article by Amar et al.1 with great interest. Their trial addressed whether N-acetylcysteine can prevent atrial fibrillation after thoracic surgery. A secondary analysis examined perioperative systemic markers of inflammation, oxidative stress, and the incidence of atrial fibrillation after discharge. We thank the authors for contributing to our understanding on this important topic. However, we have two questions regarding subgroup analysis.First, the primary endpoint analysis included surgical procedures such as open thoracotomy, minimally invasive video-assisted thoracoscopic, robotic-assisted approaches, and Ivor Lewis esophagectomy. However, there was not a subgroup analysis by surgical modality. Of note, the incidence of postoperative atrial fibrillation is influenced by the extent of lung resection2 and by the operative site (left more than right lobectomy).3 Moreover, lobectomy removes more lung tissue than segmentectomy, which may induce myocardial hypoxia, thereby triggering atrial fibrillation.2,4 A subgroup analysis of N-acetylcysteine effect according to surgical approach may be informative.Second, the conclusion that N-acetylcysteine did not result in lower systemic markers of inflammation and oxidative stress should be interpreted with caution given the lack of power to identify these secondary outcomes. Perioperative drugs such as opioids and dexmedetomidine may affect intraoperative stress and inflammatory response. Oxycodone, for instance, has antioxidant and anti-inflammatory properties that protect against surgical stress by inhibiting the production of proinflammatory cytokines and lipid peroxidation.5 Therefore, it would be of interest to perform a more comprehensive analysis of potential pharmacologic influence on the results.Postoperative atrial fibrillation is an important clinical outcome in patients undergoing noncardiac thoracic surgery, and there is growing interest in its prevention and treatment. However, multiple factors contribute to postoperative atrial fibrillation and inflammatory response. If there is substantial heterogeneity of these risk factors in the study population, risk-stratified analysis is especially important for enhancing the credibility of clinical trials.Supported by Zhongshan City Social Welfare project No. 2020B1002.The authors declare no competing interests.

Impact of rs11024102 PLEKHA7, rs3753841 COL11A1 single nucleotide polymorphisms, and serum levels of oxidative stress markers on the risk of primary angle-closure glaucoma in Egyptians

BackgroundPrimary angle-closure glaucoma (PACG) is one of the major causes of blindness in the Middle East with genetic loci and systemic oxidative stress as potential risk factors. The current case-control study aimed to investigate the associations of rs11024102 in Pleckstrin homology domain-containing family A member 7 (PLEKHA7), rs3753841 in collagen 11 A1 (COL11A1), and the systemic oxidative stress markers with PACG in Egyptian patients. Thirty-five control subjects and 64 PACG patients were enrolled in this study. The polymorphisms in PLEKHA7 and COL11A1 were analyzed using quantitative PCR, and their associations were statistically tested with PACG at homozygous, heterozygous, dominant, and recessive genetic models. The levels of malondialdehyde (MDA), advanced glycation-end product (AOPP), protein carbonyl (PC), and ischemia modified albumin (IMA) were quantitated colorimetrically, and their associations with PACG were analyzed statistically. The associations of MDA, AOPP, PC, and IMA with elevated intraocular pressure (IOP) were statistically tested. ResultsNeither significant difference in the genotype distribution nor allele frequency of PLEKHA7 11024102 T>C (p = 0.425 and 0.517, respectively) and COL11A1 rs3753841 G>A (p = 0.600 and 0.473, respectively) were recorded under any of the tested genetic models. Either rs11024102 PLEKHA7 or rs3753841 COL11A1 was not significantly (p > 0.025 after Bonferroni correction) associated with an increased risk of PACG in Egyptians. Egyptian patients with PACG showed significant elevations in the serum levels of MDA, AOPP, and PC either in patients with or without cases with diabetes mellites, hypertension, coronary vascular diseases, and smoking. Serum levels of MDA, AOPP, and PC were significantly associated with PACG in Egyptians (p < 0.013 after Bonferroni correction). However, MDA and PC only showed significant associations with the elevation in the IOP (p = 0.007 and 0.045, respectively) in PACG patients. ConclusionBoth rs11024102 and rs3753841 could not be considered as potential gene-dependent risk factors for PACG pathogenesis in Egyptians. On the other hand, serum levels of MDA, AOPP, and PC might be considered risk factors for PACG. Moreover, MDA and PC could serve as good predictors for the elevation of the IOP in PACG disease.