Erythrocyte Glutathione Research Articles

The status of erythrocyte glutathione in clinical medicine: reality and possibilities

The review examines the current state of free radical oxidation processes in clinical medicine. Based on many years of our research and analysis of the literature, we consider the most promising assessment of the activity of glutathione reductase and the level of glutathione reduced in erythrocytes, as a characteristic of the thiol-disulfide redox system of glutathione, not only to indicate oxidative stress, but also a possible prognostic marker of “free radical diseases”.

Oxidative stress-related biomarkers as promising indicators of inflammatory bowel disease activity: A systematic review and meta-analysis

Oxidative stress is believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD), specifically Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis aimed to identify and quantify the oxidative stress-related biomarkers in IBD and their associations with disease activity. We systematically searched Ovid MEDLINE, Ovid Embase, and Web of Science databases, identifying 54 studies for inclusion. Comparisons included: (i) active IBD versus healthy controls; (ii) inactive IBD versus healthy controls; (iii) active CD versus inactive CD; and (iv) active UC versus inactive UC. Our analysis revealed a significant accumulation of biomarkers of oxidative damage to biomacromolecules, coupled with reductions in various antioxidants, in both patients with active and inactive IBD compared to healthy controls. Additionally, we identified biomarkers that differentiate between active and inactive CD, including malondialdehyde, Paraoxonase 1, catalase, albumin, transferrin, and total antioxidant capacity. Similarly, levels of Paraoxonase 1, erythrocyte glutathione peroxidase, catalase, albumin, transferrin, and free thiols differed between active and inactive UC. Vitamins and carotenoids also emerged as potential disease activity biomarkers for CD and UC, but their intake should be monitored to obtain meaningful results. These findings emphasize the involvement of oxidative stress in the pathogenesis of IBD and highlight the potential of oxidative stress-related biomarkers as a minimally invasive and additional tool for monitoring the activity of IBD.

Magnesium, selenium and zinc deficiency compromises antioxidant defense in women with obesity.

Studies have shown that deficiencies in magnesium, selenium, and zinc in individuals with obesity compromise the endogenous antioxidant defense system. This study aimed to evaluate the impact of mineral deficiency on enzymatic antioxidant defense in women with obesity. The study involved 63 women with obesity (BMI ≥ 35kg/m2) and 77 eutrophic women (BMI between 18.5 and 24.9kg/m2). Variables such as fasting glucose, glycated hemoglobin, fasting insulin, and serum lipids were analyzed. Insulin resistance was measured using the homeostasis assessment model (HOMA-IR) and beta cell function using the homeostasis assessment model (HOMA-β). Dietary intake of energy, macronutrients (including magnesium, zinc, and selenium), and plasma, erythrocyte, and urinary concentrations of these minerals were measured and analyzed. Serum cortisol, plasma leptin, plasma thiobarbituric acid reactive substances, and the activity of erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPX), and erythrocyte catalase were also analyzed. Women with obesity had reduced plasma and erythrocyte concentrations and greater urinary excretion of all minerals compared to normal weight women (p < 0.05). There was a positive association between erythrocyte concentrations of zinc and selenium and the activity of the GPX and SOD enzymes in erythrocytes in women with obesity (p < 0.05), in addition to a positive association between serum insulin and the enzyme GPX, which is dependent on dietary selenium (p < 0.05). Individuals with obesity are deficient in magnesium, selenium, and zinc, which appears to impair the antioxidant defense system and contribute to important metabolic disorders such as oxidative stress in these patients.

Effect of N-acetyl cysteine in children with metabolic dysfunction-associated steatotic liver disease-A pilot study.

Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), and its sequelae of more severe forms such as metabolic dysfunction-associated steatohepatitis (MASH) is rapidly increasing in children with the rise in obesity. Successful and sustainable treatments for MASLD are lacking in children. We determined the therapeutic effect of N-acetyl cysteine (NAC) on biomarkers of oxidative stress, inflammation and insulin resistance (IR), liver enzymes, liver fat fraction (LFF) and liver stiffness (LS) in children with obesity and biopsy-confirmed MASLD. Thirteen children (n = 13; age: 13.6 ± 2.8 years; NAS score >2) underwent a double-blind, placebo-controlled trial of NAC (either 600 or 1200 mg NAC/day) or placebo for 16 weeks. Measurements included LFF (magnetic resonance imaging), LS (ultrasound elastography), and body composition. Erythrocyte glutathione (GSH), liver enzymes, insulin, glucose, adiponectin, high-sensitivity c-reactive protein (hs-CRP), and interleukin-6 (IL-6) were also measured. homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. Sixteen-week NAC treatment improved (baseline adjusted between-group p < .05 for all) markers of inflammation (IL-6 and hs-CRP), oxidative stress (GSH), and IR (HOMA-IR) and reduced liver enzymes, LFF and LS. Body weight and body composition did not show beneficial changes. Sixteen-week NAC treatment was well tolerated in children with obesity and MASLD and led to improvements in oxidative stress, inflammation and IR and liver outcomes. The results from this pilot study support further investigation of NAC as a therapeutic agent in children with MASLD.

Serum Total Bilirubin and Oxidative Stress Status in Diabetic Retinopathy – A Hospital-Based Observational Study

Diabetic retinopathy (DR) is one of the common microvascular complications of Type 2 Diabetes Mellitus (T2DM). As an antioxidant, the serum total bilirubin is associated with vaso-occlusive disorders. Oxidative stress parameters such as Erythrocyte Glutathione (GSH) as an antioxidant and Malondialdehyde (MDA) as an oxidant are critical in the pathogenesis of diabetic complications. This study aimed to explore the possibilities of the endogenous protective role of serum total bilirubin on the retinal vasculature in DR patients by estimating and correlating the levels of serum total bilirubin, GSH, and MDA in DR cases. In this hospital-based case-control study, 288 participants were selected from R.L. Jalappa Hospital and Research Centre, Kolar, divided into three groups with 96 subjects per group. Group I: Controls, Group II: T2DM, and Group III: DR subjects. The fasting blood sugar, glycated hemoglobin, liver function test, and lipid profiles were estimated by standard methods. Oxidative stress parameters viz, GSH and MDA were assayed by chromogen 5,5'- di thiobis 2-nitrobenzoic acid (DTNB) and thiobarbituric acid reactive substances (TBARS) methods, respectively. The prevalence of DR was significantly lower among subjects with the highest bilirubin quartile than those with the lowest. There was a significant mean difference with p&lt;0.001 between the groups for total bilirubin, FBS, HbA1c, GGT, TC, TG, LDL, GSH, and MDA. A Negative correlation of serum total bilirubin with FBS (r = - 0.375), HbA1c (r = -0.351), and MDA(r=-0.323), and a positive correlation with GSH (r = 0.335) was observed in DR group with a significant p-value. T2DM subjects with higher levels of bilirubin within biological reference intervals were less likely to develop retinopathy. The severity of DR was inversely proportional to the total bilirubin levels. Therefore, serum total bilirubin levels could be a biomarker to predict the risk of developing retinopathy in people with T2DM.

Impact of Adherence to the Mediterranean Diet on Antioxidant Status and Metabolic Parameters in NAFLD Patients: A 24-Month Lifestyle Intervention Study.

The Mediterranean Diet (MedDiet) is recognized as a healthy dietary pattern. Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in the liver. To assess the antioxidant status in erythrocytes, plasma, and peripheral blood mononuclear cells (PBMCs) of NAFLD patients following a 24-month lifestyle intervention based on the MedDiet. Adult patients (n = 40; aged 40-60 years) diagnosed with NAFLD by magnetic resonance imaging were divided into two groups based on their adherence to the MedDiet. Consumption was assessed using a validated 143-item semiquantitative Food Frequency Questionnaire. Anthropometrics, biochemistry parameters, intrahepatic fat contents (IFC), antioxidants, and inflammatory biomarkers were measured in plasma and erythrocytes before and after the intervention. After the intervention, body mass index (BMI) and plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-chol), triglycerides, malondialdehyde (MDA), and cytokeratin-18 (CK18) decreased, and high-density lipoprotein cholesterol (HDL-chol) increased. Participants with high adherence to MedDiet showed lower IFC, hepatic enzyme (AST, ALT, and GGT), glycemia, oxidase LDL (oxLDL) plasma levels, and erythrocyte MDA levels. Higher antioxidant activity (erythrocyte catalase-CAT, superoxide dismutase-SOD, glutathione peroxidase-GPx, glutathione reductase-GRd, and total glutathione-GSH as well as PBMCs-CAT gene expression) was observed in these patients, along with a reduction of PBMCs reactive oxygen species production and Toll-like receptor 4 (TLR4) expression. Inverse associations were observed between adherence to the MedDiet and BMI, glycemia, AST, IFC, and CK18 plasma levels and oxLDL, CAT, SOD, and GRd activities in erythrocytes. A significant linear regression was observed between adherence to the MedDiet and antioxidant score. Adherence to the MedDiet is associated with improved plasma and PBMC antioxidant and inflammatory biomarker profiles and high antioxidant defences in erythrocytes.

Assessment of oxidative stress parameters in summer anestrous buffaloes exhibiting differential fertility following melatonin implants treatment

For evaluating the impact of melatonin implants treatment during non-breeding season to ameliorate oxidative stress, 132 anestrous buffaloes were subcutaneously inserted with 2x4 mm absorbable slow-release melatonin implants (18 mg/50 kg b wt) at the base of left ear and 60 buffaloes were used as control. Ovarian ultrasonography and jugular vein blood sampling were carried out at 7-day interval till day 35 post-treatment or till ovulation, whichever was earlier. Control and implanted buffaloes were subjected to artificial insemination (AI) at overt or induced estrus followed by pregnancy diagnosis at day 90 post-AI. Erythrocytic lipid peroxidation (LPO) values were reduced (P&lt;0.05) in implanted buffaloes from day 21 post-treatment onwards when compared to their pre-treatment and Control group values. However, the concentrations of erythrocytic glutathione peroxidase (GPx), glutathione reductase and superoxide dismutase (SOD) were invariably higher (P&lt;0.05) following treatment as compared to their pre-treatment and Control group values. The buffaloes ovulating in Control or Treatment group revealed higher (P&lt;0.05) erythrocytic GPx in the Latter group. Also, between pregnant counterparts of Control and Treatment group, the Latter group buffaloes exhibited low (P&lt;0.05) erythrocytic LPO, and high (P&lt;0.05) erythrocytic GPx, SOD and catalase. It can be concluded that melatonin implants treatment was successful for mitigating the oxidative stress in summer anestrous buffaloes, and the status of oxidative stress parameters following treatment was better in buffaloes that ovulated or conceived subsequently.

Erythrocyte Glutathione S-Transferase Activity as a Sensitive Marker of Kidney Function Impairment in Children with IgA Vasculitis.

IgA vasculitis (IgAV) is the most common childhood vasculitis. The main cause of morbidity and mortality in children with IgAV is nephritis (IgAVN), but the risk of its development, severity, and chronicity remain unclear. Erythrocyte glutathione S-transferase (e-GST) activity has been previously detected as a sensitive marker of kidney function impairment in several diseases. We spectrophotometrically assessed and correlated e-GST activity between 55 IgAV patients without nephritis (IgAVwN), 42 IgAVN patients, and 52 healthy controls. At disease onset, e-GST activity was significantly higher in IgAVN patients (median (interquartile range)) (5.7 U/gHb (4.4-7.5)) than in IgAVwN patients (3.1 U/gHb (2.2-4.2); p < 0.001), and controls (3.1 U/gHb (1.9-4.2); p < 0.001). Therewithal, there were no differences between the IgAVwN patients and controls (p = 0.837). e-GST activity was also significantly higher in the IgAVN patients than in the IgAVwN patients after 3 months (5.0 U/gHb (4.2-6.2) vs. 3.3 U/gHb (2.3-4.1); p < 0.001) and 6 months (4.2 U/gHb (3.2-5.8) vs. 3.3 U/gHb (2.1-4.1); p < 0.001) since the disease onset. Consistent correlations between e-GST activity and serum creatinine, estimated glomerular filtration rate (eGFR), and proteinuria levels were not detected. In conclusion, increased e-GST activity can serve as a subtle indicator of kidney function impairment in children with IgAV.

Glycine supplementation can partially restore oxidative stress-associated glutathione deficiency in ageing cats.

Intracellular levels of glutathione, the major mammalian antioxidant, are reported to decline with age in several species. To understand whether ageing affects circulating glutathione levels in cats, blood was sampled from two age groups, < 3 years and > 9 years. Further, to determine whether dietary supplementation with glutathione precursor glycine (GLY) affects glutathione concentrations in senior cats (> 8 years), a series of free GLY inclusion level dry diets were fed. Subsequently, a 16-week GLY feeding study was conducted in senior cats (> 7 years), measuring glutathione, and markers of oxidative stress. Whole blood and erythrocyte total, oxidised and reduced glutathione levels were significantly decreased in senior cats, compared with their younger counterparts (P ≤ 0·02). The inclusion level study identified 1·5 % free GLY for the subsequent dry diet feeding study. Significant increases in erythrocyte total and reduced glutathione were observed between senior cats fed supplemented and control diets at 4 weeks (P ≤ 0·03; maximum difference of 1·23 µM). Oxidative stress markers were also significantly different between groups at 8 (P = 0·004; difference of 0·68 nG/ml in 8-hydroxy-2'-deoxyguanosine) and 12 weeks (P ≤ 0·049; maximum difference of 0·62 nG/mG Cr in F2-isoprostane PGF2α). Senior cats have lower circulating glutathione levels compared with younger cats. Feeding senior cats a complete and balanced dry diet supplemented with 1·5 % free GLY for 12 weeks elevated initial erythrocyte glutathione and altered markers of oxidative stress. Dietary supplementation with free GLY provides a potential opportunity to restore age-associated reduction in glutathione in cats.

Protein intake affects erythrocyte glutathione synthesis in healthy adults aged ≥60 years in a repeated-measures trial

BackgroundProtein recommendations for older adults are based on nitrogen balance data from young adults. Physiological studies using the indicator amino acid oxidation method suggest they need 30% to 50% more protein than current recommendations. We herein present glutathione (GSH) as a physiological estimate of protein adequacy in older adults. ObjectivesThe objective was to measure GSH kinetics in response to varying protein intakes in a repeated-measures design in healthy adults aged ≥60 y using the precursor-product method. MethodsSixteen healthy older adults (n = 8 male and n = 8 female; body mass index ≤30 kg/m2) were studied. Each received 4 of 6 protein intakes in random order (0.66, 0.8, 0.9, 1.1, 1.3 and 1.5 g⋅kg−1⋅d−1). At each intake level, participants underwent isotope infusion studies of 7 h duration following a 3-d adaptation to the test level of protein. On the fourth day, GSH fractional (FSR) and absolute synthesis (ASR) rates were quantified by measuring the incorporation of U-[13C2-15N]glycine into GSH at isotopic steady state. A mixed-effect change-point regression model was used to determine a breakpoint in FSR and ASR. Secondary outcomes included plasma concentrations of oxidative stress markers, homocysteine, 5-L-oxoproline (5-OP), and urinary sulfate. The effect of secondary outcomes on GSH kinetics was analyzed using a joint linear mixed-effect model and Tukey’s post hoc test. ResultsA protein intake of 1.08 g⋅kg−1⋅d−1 (95% confidence interval [CI]: 0.83, 1.32; Rm2 = 0.207; Rc2 = 0.671; P < 0.001) maximized GSH FSR. There was no effect of protein intake on concentrations of erythrocyte GSH, plasma homocysteine, oxidative stress markers, or 5-OP (P > 0.05). Protein intake had a positive effect on urinary sulfate excretion (P < 0.0001). ConclusionA protein intake of 1.08 g⋅kg−1⋅d−1 from a high-quality protein maximized GSH synthesis in adults ≥60 y. This lends support to data suggesting a requirement higher than the current recommendation.This study was registered at clinicaltrials.gov as NCT02971046.

The role of serum bilirubin in the pathogenesis of Crohn’s disease in children and assessment of its activity

Introduction. The article is devoted to the identification of a marker of imbalance of oxidative stress and the antioxidant system in children with Crohn’s disease. The putative level of total bilirubin as an integrative method for assessing Crohn’s disease activity is highly correlated with indicators of oxidative stress and the antioxidant system (ischemia, modifying albumin, malondialdehyde, catalase, sulfhydryl groups and glutathione). Purpose: to explain the relationship between the level of total bilirubin and the activity of the inflammatory process in Crohn’s disease, which allows the introduction of the studied integrative indicator in clinical practice. Materials and methods. Based on the results of scientific studies of biomarkers of oxidative stress (albumin-modifying ischemia - plasma IMA, malondialdehyde - plasma MDA) and the antioxidant system (plasma SH-groups, catalase and reduced erythrocyte glutathione), as well as a simultaneous study of the level of total bilirubin in children diagnosed with Crohn’s disease. To search for a differential method for assessing the level of Crohn’s disease activity by the degree of bilirubin, use binary logistic regression. Results and survey. The results of the study showed a clear relationship between the increase in bilirubin levels and the severity of oxidative stress. It has been established that with a decrease in the level of total bilirubin, there is a predominance of oxidative stress over the antioxidant system, which leads to an increase in inflammation activity. It has been proven that the level of total bilirubin can be used in the complex activity of diseases as a minimally invasive, as well as an objective and acute marker. The sensitivity and specific sensitivity of this protocol is 90.9% and 93.3% respectively, which allows the use of total bilirubin as a marker of inflammation in Crohn’s disease.

Late onset psychosis treatment with adjunctive medicines.

A number of studies have shown the feasibility of using adjunctive drugs in late onset psychosis (LOP). Testing hypothesis that among LOP people treated with antipsychotics and antidepressants, basing on certain clinical characteristics a subgroup of patients might be distinguished, for whom adjunctive therapy is advantageous. This subgroup might be identified by measurement of blood biochemical parameters. 59 in-patients with LOP, treated neuroleptics and antidepressants, were included, and followed in real clinical practice. Database containing demographic, clinical data (scores by PANSS, CDSS, CGI-S, HAMD-17), prescribed therapy, adverse effects of antipsychotic and antidepressant treatment, and blood biochemical parameters (enzymatic activities of glutamate- and glutathione metabolism enzymes in platelets and erythrocytes) at baseline and after the treatment course was created. Three groups of patients (Gr1, Gr2, and Gr3), based on the adjunctive therapy usage were identified: Gr1 (n = 16) was without adjunctive therapy, two other groups (Gr2 and Gr3) were with adjunctive medicines, such as 2-ethyl-6-methyl-3-hydroxypyridine succinate (EMHS; Gr2, n = 20), or other drugs, such as citicoline, cerebrolysin, cortexin, actovegin, gliatilin (choline alfoscerate; Gr3, n = 23). The enzymatic activities were assessed also in the matched control group (n = 38). In all three patient groups, as compared with controls, activity of erythrocyte glutathione reductase was decreased at baseline and after the treatment course. In Gr2, unlike Gr1 or Gr3, there was a significant decrease in baseline glutamate dehydrogenase and glutathione-S-transferase activities. Certain clinical criteria were also elucidated for prescription of EMHS as adjunctive therapy for patients of Gr2. Glutamate dehydrogenase and glutathione-S-transferase activities returned closer to control levels after the treatment course in Gr2, unlike Gr1, where they declined yet more after psychotropic treatment without adjunctive medicine. Different significant links between biochemical parameters and scores by clinical scales were observed in Gr1, Gr2, and Gr3, some having predictive value for evaluation of antipsychotic treatment efficacy. We demonstrate the validity of adjunctive neuroprotective medicines' usage in addition to antipsychotic and antidepressant therapy in distinct subgroups of patients suffering with LOP, especially those who have prominent side effects accompanying their psychotropic treatment. Returning of biochemical parameters to control range following the treatment course observed in patients of the subgroup treated with adjunctive EMHS is evidence for their metabolism normalization.

Systematic review and meta-analysis of oxidative stress and antioxidant markers in recurrent aphthous stomatitis

BackgroundWe performed this systematic review and meta-analysis to synthesize all studies that reported the level of oxidative and antioxidative markers in recurrent aphthous stomatitis (RAS) patients compared to controls.MethodsWe registered our study in PROSPERO (CRD42023431310). PubMed, ProQuest, Scopus, EMBASE, Google Scholar, and Web of Science were searched to find relevant publications up to June 5, 2023. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. We included 30 articles after multiple stags of screening.ResultsWe found that erythrocyte superoxide dismutase and Glutathione peroxidase activity were significantly lower in patients with RAS compared to healthy controls (SMD = − 1.00, 95%CI = -1.79 to -0.21, p = 0.013, and SMD = − 1.90, 95%CI = -3.43 to -0.38, p = 0.01, Respectively). However, there was not any difference between patients with RAS and healthy controls in erythrocyte Catalase (SMD = − 0.71, 95%CI = -1.56–0.14, p = 0.10). The total antioxidant status (TAS) level, in serum was significantly lower in patients than healthy controls (SMD = − 0.98, 95%CI = -1.57 to -0.39, p = 0.001). In addition, RAS patients had higher levels of serum Malondialdehyde (MDA), Serum total oxidant status, and serum oxidative stress index than healthy controls (SMD = 2.11, 95%CI = 1.43–2.79, p < 0.001, SMD = 1.53, 95%CI = 0.34–2.72, p = 0.01, and SMD = 1.25, 95%CI = 0.25–2.25, p = 0.014, Respectively); However, salivary MDA and TAS, and serum uric acid, vitamin E and C, and reduced glutathione levels of patients with RAS were not different from that of healthy controls.ConclusionsThe relationship between oxidative stress and RAS is well established in this meta-analysis. Although the molecular processes underlying the etiology of this pathology remain unknown, evidence indicating oxidative stress has a significant role in the pathogenesis of RAS has been revealed.

Protein intake affects erythrocyte glutathione synthesis in young healthy adults in a repeated-measures trial

BackgroundIn 2005, the Institute of Medicine advised using methods other than nitrogen balance (NB) for determining protein requirements. Since then, protein requirements using indicator amino acid oxidation (IAAO) have been published and are higher than NB. Glutathione (GSH), a tripeptide of cysteine, glutamate, and glycine, is a principal antioxidant that can be used as a functional indicator of protein adequacy. ObjectivesThe aim of this study was to measure changes in erythrocyte GSH kinetics [fractional synthesis rate (FSR) and absolute synthesis rate (ASR)] in healthy adults following a range of protein intakes at and above the current recommendations. MethodsSixteen healthy adults [8 males and 8 females, aged 25.6 ± 0.9 y (mean ± SEM)] were studied at 4 of 6 protein intakes ranging from 0.6 to 1.5 g⋅kg-1⋅d-1. Erythrocyte GSH kinetics were assessed during a 7-h infusion of [U-13C2–15N]glycine following 2 d of adaptation to each protein intake. Blood and urine tests were performed to measure oxidative stress markers, plasma homocysteine, triglycerides, plasma amino acid concentrations, 5-L-oxoproline (5-OP), and urinary sulfate. The protein intake that maximized GSH synthesis was determined using mixed-effect change-point regression in R. Primary and secondary outcomes were analyzed using linear mixed-effects and repeated-measures analysis of variance with Tukey’s post hoc test. ResultsThe protein intake that maximized GSH FSR at 78%⋅d-1 was 1.0 g⋅kg-1⋅d-1 (95% confidence interval: 0.63, 1.39). GSH ASR was significantly lower at 0.6 and 0.8 g⋅kg-1⋅d-1 than at 1.5 g⋅kg-1⋅d-1 (2.03 and 2.17, respectively, compared with 3.71 mmol⋅L-1⋅d-1). Increasing the protein intake led to increased urinary sulfate but did not affect erythrocyte GSH concentration, plasma oxidative stress markers, triglycerides, homocysteine, or 5-OP. ConclusionsA protein intake of 1.0 g⋅kg-1⋅d-1 maximized GSH synthesis, which is in agreement with earlier IAAO-derived protein requirements of 0.93 to 1.2 g⋅kg-1⋅d-1. These findings suggest that recommendations based on NB (0.66 g⋅kg-1⋅d-1) may underestimate protein needs for adequate health.This trial was registered at clinicaltrials.gov as NCT02971046.

Redox imbalance in patients with heart failure and ICD/CRT-D intervention. Can it be an underappreciated and overlooked arrhythmogenic factor? A first preliminary clinical study.

Introduction: Redox imbalance and oxidative stress are involved in the pathogenesis of arrhythmias. They also play a significant role in pathogenesis of heart failure (HF). In patients with HFand implanted cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D), the direct current shocks may be responsible for additional redox disturbances and additionally increase arrhythmia risk. However, the precise role of oxidative stress in potentially fatal arrhythmias and shock induction remains unclear. Methods: 36 patients with diagnosed HF and implanted ICD/CRT-D were included in this study. Patients were qualified to the study group in case of registered ventricular arrhythmia and adequate ICD/CRT-D intervention. The control group consisted of patients without arrhythmia with elective replacement indicator (ERI) status. Activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) in erythrocyte (RBC), SOD, GPx activity and reactive oxygen/nitrogen species (ROS/RNS) concentration in plasma were determined. The values were correlated with glucose, TSH, uric acid, Mg and ion concentrations. Results: In the perishock period, we found a significant decrease in RBC and extracellular (EC) SOD and RBC CAT activity (p = 0.0110, p = 0.0055 and p = 0.0002, respectively). EC GPx activity was also lower (p = 0.0313). In all patients, a decrease in the concentration of all forms of glutathione was observed compared to the ERI group. Important association between ROS/RNS and GSH, Mg, TSH and uric acid was shown. A relationship between the activity of GSH and antioxidant enzymes was found. Furthermore, an association between oxidative stress and ionic imbalance has also been demonstrated. The patients had an unchanged de Haan antioxidant ratio and glutathione redox potential. Conclusion: Here we show significant redox disturbances in patients with HF and ICD/CRT-D interventions. Oxidative stress may be an additional risk factor for the development of arrhythmia in patients with HF. The detailed role of oxidative stress in ventricular arrhythmias requires further research already undertaken by our team.

IMPACT OF VITAMIN E AND SELENIUM INTAKE ON ANTIOXIDANT PROTECTION INDICATORS DURING PHYSICAL EXERTION IN INDIVIDUALS WITH HYPERTENSION

Hypertension remains one of the main problems in modern medicine since it is a pathogenetic factor leading to a large number of cardiovascular diseases and premature death.&#x0D; The aim of the study is to measure and compare the levels of sulfhydryl groups in plasma and blood as well as reduced glutathione of erythrocytes in patients with stage II hypertension before and after engaging in a controlled physical exercise taking into account the intake of vitamin E and selenium.&#x0D; Material and Methods. There were 60 patients with stage II hypertension and 30 relatively healthy individuals. The individuals under observation performed a two-stage physical exercise on a stationary bicycle ergometer with the intensity, corresponding to 50 and 75% of the maximum oxygen consumption by the body. The overall duration of each stage of the physical exercise accounted for 5 minutes with a three-minute break to rest in between. Blood was taken from the ulnar vein before the cardiac stress test and 5 minutes after it. The content of sulfhydryl groups in plasma and erythrocytes, as well as reduced glutathione of erythrocytes was measured in patients before and after the physical exercise. The examination was conducted twice - before and after the intake of vitamin E and selenium.&#x0D; Results and Discussion. Since the immediate response to a cardiac stress test performed on a stationary bicycle is shown by changes in the level of non-protein-bound sulfhydryl groups of erythrocytes (the level decreases), it can be assumed that they are involved in the formation of the primary compensatory reaction in response to physical exercise in individuals suffering from arterial hypertension.&#x0D; Conclusion. Thus, the decrease in the level of non-protein-bound sulfhydryl groups of erythrocytes enables to assess the degree of stress that affects the human body, as well as the antioxidant protection enhancement in patients with hypertension after taking vitamin E and selenium both before and after engaging in physical exercise.

Risk factors for anaemia among women and their young children hospitalised with suspected thiamine deficiency in northern Lao PDR.

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao People's Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to <18 months) with clinical symptoms suggestive of thiamine deficiency disorders were eligible along with their mothers. Venous blood was collected for determination of haemoglobin, ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), erythrocyte glutathione reductase activation coefficient (EGRac), thiamine diphosphate (ThDP) and acute phase proteins. Risk factors for anaemia were modelled using minimally adjusted logistic regression controlling for age. Haemoglobin results were available for 436 women (mean ± SD age 24.7 ± 6.4 years; 1.6% pregnant) and 427 children (4.3 ± 3.5 months; 60.3% male). Anaemia prevalence (Hb < 120 g/L for nonpregnant women and <110 g/L for pregnant women and children) was 30.7% among women and 55.2% among children. In bivariate analyses, biomarkers significantly associated with anaemia in women were ferritin, sTfR, RBP, EGRacand ThDP. Other risk factors for women were lower BMI, mid-upper arm circumference < 23.5 cm, lower education, lower socioeconomic index, food insecurity, Hmong ethnicity, not/rarely having attended antenatal care, not having taken antenatal iron-containing supplements and not meeting minimum dietary diversity. Risk factors for anaemia among children were older age, male sex, stunting, sTfR, ThDPand alpha-1-acid-glycoprotein. Anaemia was common among women and their hospitalised children and was associated with micronutrient deficiencies and socioeconomic,dietary and health care-seeking risk factors, suggesting that multiple strategies are required to prevent anaemia among women and children.

Changes to insulin sensitivity in glucose clearance systems and redox following dietary supplementation with a novel cysteine-rich protein: A pilot randomized controlled trial in humans with type-2 diabetes

We recently developed a novel keratin-derived protein (KDP) rich in cysteine, glycine, and arginine, with the potential to alter tissue redox status and insulin sensitivity. The KDP was tested in 35 human adults with type-2 diabetes mellitus (T2DM) in a 14-wk randomised controlled pilot trial comprising three 2×20 g supplemental protein/day arms: KDP-whey (KDPWHE), whey (WHEY), non-protein isocaloric control (CON), with standardised exercise. Outcomes were measured morning fasted and following insulin-stimulation (80 mU/m2/min hyperinsulinaemic-isoglycaemic clamp). With KDPWHE supplementation there was good and very-good evidence for moderate-sized increases in insulin-stimulated glucose clearance rate (GCR; 26%; 90% confidence limits, CL 2%, 49%) and skeletal-muscle microvascular blood flow (46%; 16%, 83%), respectively, and good evidence for increased insulin-stimulated sarcoplasmic GLUT4 translocation (18%; 0%, 39%) vs CON. In contrast, WHEY did not effect GCR (-2%; -25%, 21%) and attenuated HbA1c lowering (14%; 5%, 24%) vs CON. KDPWHE effects on basal glutathione in erythrocytes and skeletal muscle were unclear, but in muscle there was very-good evidence for large increases in oxidised peroxiredoxin isoform 2 (oxiPRX2) (19%; 2.2%, 35%) and good evidence for lower GPx1 concentrations (-40%; -4.3%, -63%) vs CON; insulin stimulation, however, attenuated the basal oxiPRX2 response (4%; -16%, 24%), and increased GPx1 (39%; -5%, 101%) and SOD1 (26%; -3%, 60%) protein expression. Effects of KDPWHE on oxiPRX3 and NRF2 content, phosphorylation of capillary eNOS and insulin-signalling proteins upstream of GLUT4 translocation AktSer437 and AS160Thr642 were inconclusive, but there was good evidence for increased IRSSer312 (41%; 3%, 95%), insulin-stimulated NFκB-DNA binding (46%; 3.4%, 105%), and basal PAK-1Thr423/2Thr402 phosphorylation (143%; 66%, 257%) vs WHEY. Our findings provide good evidence to suggest that dietary supplementation with a novel edible keratin protein in humans with T2DM may increase glucose clearance and modify skeletal-muscle tissue redox and insulin sensitivity within systems involving peroxiredoxins, antioxidant expression, and glucose uptake.

Arsenic exposure and increased C-reactive protein are independently associated with lower erythrocyte glutathione peroxidase activity in Bangladeshi children

Toxic metal contaminants present in food and water have widespread effects on health and disease. Chalcophiles, such as arsenic, cadmium, and mercury, show a high affinity to selenium and exposure to these metals could have a modulating effect on enzymes dependent on selenocysteine in their active sites. The aim of this study was to assess the influence of these metals on the activity of the selenoprotein glutathione peroxidase 1 (GPX1) in erythrocytes of 100 children residing in rural Bangladesh, where drinking water often contains arsenic. GPX1 expression, as measured using high-throughput immunoblotting, showed little correlation with GPX activity (rs = 0.02, p = 0.87) in blood samples. Toxic metals and selenium measured in erythrocytes using inductively coupled plasma mass spectrometry (ICP-MS) and C-reactive protein (CRP) measured in plasma, were all considered as effectors of this divergence in GPX enzymatic activity. Arsenic concentrations in erythrocytes were most influential for GPX1 activity (rs = −0.395, p < 0.0001), and CRP levels also negatively impacted GPX1 activity (rs = −0.443, p < 0.0001). These effects appear independent of each other as arsenic concentrations and CRP showed no correlation (rs = 0.124, p = 0.2204). Erythrocyte selenium, cadmium, and mercury did not show any correlation with GPX1 activity, nor with CRP or arsenic. Our findings suggest that childhood exposure to inorganic arsenic, as well as inflammation triggering the release of CRP, may negatively affect GPX1 activity in erythrocytes.

Oxidative stress markers cannot be used as endometriosis biomarkers in infertile patients

Objectives Endometriosis is a common benign gynaecological disease that significantly compromises the quality of life of patients. To date, invasive surgery is the method of choice to visually and histologically confirm endometriosis. Thus, there is a major interest to develop noninvasive diagnostic tools. Oxidative stress is one of the proposed mechanisms of pathogenesis and may be involved in pelvic pain, dysmenorrhea, dyspareunia, and infertility in endometriosis patients. Thus, markers of oxidative stress may serve as diagnostic biomarkers for endometriosis. Design This prospective case–control study assessed erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPX), serum hexanoyl lysine (HEL) and peritoneal fluid HEL. Participants/Materials, Setting, and Methods We enrolled 86 women with primary infertility; the case group included 57 women with endometriosis, and the control group included 29 women with unexplained primary infertility. All the patients underwent laparoscopy, and the diagnosis was confirmed histologically. RANDOX and RANSEL reagents were used to determine the levels of SOD and GPX, respectively, and ELISA was used to determine the levels of HEL. Results We found no statistically significant differences in the erythrocyte levels of GPX (p value 0.623) or SOD (p value 0.122) or the serum or peritoneal fluid levels of HEL (p value 0.562 and 0.329 accordingly). Conclusions SOD, GPX, and HEL levels most likely do not differ between patients with unexplained infertility and patients with endometriosis.