Oxidative Stress In Erythrocytes Research Articles

Attenuation of Oxidative Stress in Erythrocytes Stored with Vitamin C and l-Carnitine in Additive Solution-7.

Background: Blood transfusion has advanced toward component therapy for specific requirements during trauma and surgery. Oxidative stress is induced in erythrocytes during storage. Hence, antioxidants as additives can be employed to counteract oxidative stress and enhance antioxidant defenses. Therefore, this study investigates the combinatorial effects of vitamin C and l-carnitine on erythrocytes during storage. Methodology: Erythrocyte samples were categorized into control and experimental groups-vitamin C (10 mM) and l-carnitine (10 mM) and stored under blood bank conditions (at 4°C) for 35 days. Hemoglobin (Hb), antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT] and glutathione peroxidase [GPX]), lipid peroxidation products (conjugate dienes and thiobarbituric acid reactive substances [TBARSs]), protein oxidation products, metabolic markers (glucose, lactate dehydrogenase), glutathione (GSH), superoxides, and hemolysis were assessed at weekly intervals. Results: SOD activity increased on day 7 in the controls, whereas it increased on days 7 and 14 in the experimental groups. CAT activity increased on day 35 in both the groups. GPX activity increased on day 7 in the controls. Hb levels decreased on days 14 and 35 in the controls and on day 35 in the experimental groups. Hemolysis increased from day 7 onward in both the groups. Protein oxidation products were maintained throughout the storage. GSH levels increased on day 21 in the controls and on days 14 and 21 in the experimental groups. Superoxides and conjugate dienes decreased from day 14 in both the groups. TBARSs decreased on day 7 in the experimental groups. Conclusion: Vitamin C and l-carnitine have synergistically enhanced the efficacy of stored erythrocytes in terms of Hb, antioxidant enzymes, and lipid peroxidation.

Erythrocyte labile iron pool indicating concealed iron overload in non-transfusion-dependent β-thalassemia

Abstract Objectives Not only do transfusion-dependent thalassemia (TDT) patients have a risk of clinical consequences arising from iron overload, non-transfusion-dependent thalassemia (NTDT) patients may encounter it also. In this study, we demonstrated the usefulness of intra-erythrocyte labile iron pool (LIP) measurement in NTDT patients with HbE/β-thalassemia in revealing a concealed iron overload and the resultant oxidative cell damage. Methods LIP and ferritin levels were assayed in 20 HbE/β-thalassemia patients, comprising 10 NTDT and 10 TDT patients and 10 healthy individuals. Erythrocyte oxidative stress parameters (intraerythrocyte reactive oxygen species (ROS) levels, numbers of erythrocyte vesicles, and cell apoptosis) were also determined and their correlations to LIP and ferritin levels were analyzed. Results LIP levels (based on different mean fluorescence intensity (MFI) values obtained by flow cytometry) were high in both the NTDT (54 [42–90]) and TDT (71 [68–77]) patients compared to the healthy individuals (43 [31–61]). The ferritin level observed in the NTDT group (2,149 [781–4,071] ng/mL) was lower than that of the TDT group (4,885 [2,343–7,826] ng/mL). The LIP level was significantly correlated with the NTDT patients’ age and all oxidative stress parameters, but the ferritin level was not. Correlation analysis predicted that NTDT patients without receiving any therapy aged 32.5 years old or over are likely at risk of iron overload status and oxidative cell damage. Conclusions The results indicate that LIP may be a helpful alternative parameter for defining the risk of iron overload.

Sodium sesquicarbonate elicits oxidative stress in erythrocytes, liver and kidney tissues

Sodium sesquicarbonate also known as Sodium sesquicarbonate dihydrate (SSD) has been used globally for centuries in food and traditional medical practices. There is paucity of scientific information on the safety of this common food additive. This study was designed to find out if the oral administration of SSD is capable of generating oxidative stress in erythrocytes, liver and kidney using albino rats as experimental models. The total number of animals used for this study was fifteen. The experimental animals were grouped into three. There were five animals in each group. The rats in the first group which was the control group, were dosed with 1 ml distilled water, while groups 2 and 3 were treated with 400 mg/kg and 800 mg/kg body weight (bw) of SSD, respectively, once daily per os for 28 days. After the duration of treatment, the erythrocytes, hepatic and kidney tissues were processed for the analysis. The biomarkers of oxidative stress, superoxide dismutase (SOD), catalase; and thiobarbituric acid reactive substances/ malondialdehyde (TBARS/MDA) were assayed. The result indicated that catalase enzyme activity was overexpressed in the red blood cells, liver and kidneys of the group that consumed the lower dose of SSD. The dose-dependent increase in the lipid peroxidation of the tissues as indicated by increased levels of MDA in the erythrocytes and TBARS in the tissues of the treated groups was significant (P < 0.05). The SOD enzyme activity in all the tissues assayed showed a dose-dependent decrease, which was significant at the probability level of 0.05. The consumption of SSD therefore caused lipid peroxidation and reduction in activity of the antioxidants present in the tissues studied.

Investigation of the toxic effects of aspartame as an artificial sweetener in food: effect on redox and inflammatory biomarkers in rat

Aspartame (L-aspartyl-L-phenylalanine methyl ester) is a widely used synthetic sweetener. The safety of aspartame consumption remains controversial due to its widespread and sometimes indiscriminate use above the FDA-recommended level. The study focused on investigating the toxic effects of aspartame administration at high doses on redox and inflammatory biomarkers in male Wistar rats. Rats were divided into two groups: Group I was given normal saline (0.9%) orally and Group II was administered with aspartame (100 mg/kg body weight) for 30 days. Administration of aspartame significantly (p<0.05) increased the levels of Malondialdehyde (MDA), protein carbonyl (PCO), and Advanced Oxidation Protein Products (AOPP) content which are prominent markers of oxidative stress. The assessment of antioxidant defenses in both the groups denoted a significant (p<0.05) decrease in levels of Ferric Reducing Ability of Plasma (FRAP), Superoxide Dismutase (SOD), and Catalase in the aspartame-treated group in comparison to the control. The proinflammatory markers Tumour Necrosis Factor -α (TNF-α), Interleukin-6 (IL-6) and C - reactive protein (CRP) were also significantly (p<0.05) increased in the treated group. These results suggest that aspartame intake of 100 mg/kg body weight contributes to oxidative stress in erythrocytes which in turn may play a role in predisposing an individual to obesity, cardiovascular disease, and cancer. Aspartame should be strictly limited to the FDA-recommended levels since its indiscriminate use causes severe toxic effects.

An Overview on Assay Methods to Quantify ROS and Enzymatic Antioxidants in Erythrocytes and Spermatozoa of Small Domestic Ruminants.

The present review aims to provide an overview of the assay methods for the quantification of ROS and principal enzymatic antioxidants as biomarkers of oxidative stress in erythrocytes and spermatozoa of small domestic ruminants. A complete literature search was carried out in PubMed, Scopus and the World Wide Web using relevant keywords and focusing on the last five years (2018-2023). Among spectrophotometry, fluorometry and chemiluminescence, the most widely used method for ROS assay is fluorometry, probably because it allows to simultaneously assay several ROS, using different probes, with greater economic advantages. Regarding intracellular antioxidant enzymes, recent literature reports only spectrophotometric methods, many of which use commercial kits. The use of a less sensitive but cheapest method is suitable because both erythrocytes and spermatozoa samples are highly concentrated in domestic ruminant species. All methods considered in this review have been found to be appropriate; in general, the differences are related to their costs and sensitivity. Quantification of ROS and enzymatic antioxidant activity in erythrocytes and spermatozoa may find application in the study of the welfare and health status of small domestic ruminants for monitoring livestock production.

Biomarkers of oxidative stress in acute blood loss and its correction with magnetite nanoparticles in a sodium chloride matrix

Among effects of magnetite (Fe3O4) nanoparticles (NPs), interest is in their ability to induce oxidative stress. The influence of magnetite NPs on the redox balance in living organisms is not unambiguous, especially against a background of experimental pathology. The purpose of this work is to study some biomarkers of oxidative stress in erythrocytes after acute blood loss with the administration of magnetite NPs in a sodium chloride (NaCl) matrix. Magnetite NPs were obtained by electron beam technology in a vacuum, characterized by standard nanoscience methods, and studied for their effect on the generation of reactive oxygen species. An NPs solution (6.75 mg Fe/kg) was administered to albino rats with acute blood loss. Biomarkers of oxidative stress in erythrocytes were determined 3, 24, 72 h and 5 days after blood loss. It was shown that the NPs condensate contained particles with an average size of 17–24 nm (TEM-SEM) and a phase composition of Fe3O4@NaCl. NPs with an average diameter of 23 nm (DLS) were present in the solution. Their ability to generate free radicals was lower than that of uncoated NPs. Acute blood loss was accompanied by the development of oxidative stress, characterized by an increase in the content of lipoperoxidation products, a decrease in the activity of superoxide dismutase and an increase in the activity of erythrocyte catalase. The Fe3O4@NaCl solution helped to reduce the manifestation of oxidative stress and accelerated restoration of the antioxidant enzymes normal activity. This indicates the promising prospects of Fe3O4@NaCl NPs in the treatment of post-hemorrhagic syndrome and requires further research.

Effects of chronic core training on serum and erythrocyte oxidative stress parameters in amputee football players.

Objective: The positive impact of aerobic exercise on blood oxidative stress parameters is well documented. However, the effect of core exercises on these parameters in amputee football players (AF) remains unclear. Therefore, this study aims to investigate the impact of core exercises on blood oxidative stress parameters in this population. Methods: Experimental method was adopted in the study. Eleven elite AF players participated in the study. The participants were divided randomly into two groups a core exercise group (CEG) and a control group (CG). Blood measurements were taken before and after the 8-week core exercise program. Blood measurements included erythrocyte Total Oxidant Status (eTOS), erythrocyte Total Antioxidant Status (eTAS), erythrocyte oxidative stress index (eOSI), serum nitric oxide (sNO), serum Total Oxidant Status (sTOS), serum Total Antioxidant Status (sTAS), serum oxidative stress index (sOSI), serum total thiol (sTT), serum native thiol (sNT), and serum disulfide (sDS) parameters were studied. Results: According to the results of the study, a significant difference was found between the 0th and eighth week pre-aerobic training load (ATL) sTOS (p = .028) values of CEG values. A significant difference was found in sTOS (p = .028) and sOSI (p = .028) values after the 0th and eighth-week pre-ATL. A significant difference was found in the sTOS (p = .043) and sOSI values (p = .043) of CG at week 0th and eighth-week pre-ATL. Conclusion: Overall, the results suggest that core exercises had a positive effect on blood oxidative stress parameters in AF players by reducing blood total oxidant levels.

Gender-specific association of SLC19A1 and MTHFR genetic polymorphism with oxidative stress biomarkers and plasma folate levels in older adults

BackgroundPlasma folate levels are closely related to antioxidant capacity and are regulated by folate pathway gene polymorphism. However, few studies have explored the gender-specific association of folate pathway gene polymorphism with oxidative stress biomarkers. The present study was designed to explore the gender-specific independent and combined impacts of solute carrier family 19 member 1 (SLC19A1) and methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms on oxidative stress biomarkers in older adults. MethodsA total of 401 subjects were recruited, including 145 males and 256 females. Demographic characteristics of the participants were collected by using a self-administered questionnaire. Fasting venous blood samples were taken for folate pathway gene genotyping, circulating lipids parameters and erythrocyte oxidative stress biomarkers measurement. The difference of genotype distribution and the Hardy-Weinberg equilibrium was calculated by the Chi-square test. The general linear model was applied to compare the plasma folate levels and erythrocyte oxidative stress biomarkers. Multiple linear regression was used to explore the correlation between genetic risk scores and oxidative stress biomarkers. Logistic regression was used to explore the association of genetic risk scores of folate pathway gene with folate deficiency. ResultsThe male subjects have lower plasma folate and HDL-C levels than the female ones, and the male carrying MTHFR rs1801133 (CC) or MTHFR rs2274976 (GA) genotypes have higher erythrocyte SOD activity. The plasma folate levels, erythrocyte SOD and GSH-PX activities were negatively correlated with genetic risk scores in the male subjects. A positive correlation between the genetic risk scores and folate deficiency was observed in the male subjects. ConclusionsThere was association between folate pathway gene polymorphism of Solute Carrier Family 19 Member 1 (SLC19A1) and Methylenetetrahydrofolate Reductase (MTHFR) with erythrocyte SOD and GSH-PX activities, and folate levels in male but not in female aging subjects. Genetic variant of genes involved in folate metabolism has strong impact on plasma folate levels in the male aging subjects. Our data demonstrated that there was a potential interaction of gender and its genetic background in affecting the body's antioxidant capacity and the risk of folate deficiency in aging subjects.

Serum and erythrocyte oxidative stress in dogs with acanthocytosis

Oxidative stress occurs as a result of an increase in oxidants and/or a reduction of antioxidants in the body, causing oxidation of cellular constituents and cellular dysfunction, which can lead to premature cell death. This study aimed to evaluate serum and red blood cell (RBC) oxidative stress in dogs with acanthocytosis. Sixteen dogs with acanthocytosis confirmed on blood smear, regardless of the associated pathological condition, and 17 healthy dogs without clinical and laboratorial alterations were selected. Complete blood counts (CBC) were performed by an automated cell counter, biochemical and oxidative stress analyzes were performed by an automated photocolorimeter. Dogs with acanthocytosis showed lower RBC, hemoglobin, hematocrit and mean corpuscular hemoglobin concentration (MCHC), and higher red cell distribution width (RDW) compared with healthy dogs. On the leukogram, higher concentrations of band neutrophils and lower numbers of lymphocytes were observed in dogs with acanthocytosis. On serum biochemical parameters, a significant increase in ALP activity, cholesterol and globulin levels, and decreased albumin concentration were observed in dogs with acanthocytosis. Regarding oxidative stress parameters, dogs with acanthocytosis showed lower serum total antioxidant capacity (TAC) by cupric reduction (TAC-CUPRAC) and higher TAC by ferric reduction (TAC-FRAP), total oxidant capacity (TOC) and lipid peroxidation, while RBC showed higher TAC by ABTS cation reduction alone (TAC-ABTS) and associated with peroxidase (TAC-ABTS+HRP), TAC-CUPRAC, TOC and lipid peroxidation compared with those of control dogs. Dogs with acanthocytosis demonstrate serum and erythrocyte oxidative stress, which may be one of the factors involved in erythrocyte damage.

Unexplored Roles of Erythrocytes in Atherothrombotic Stroke.

Stroke constitutes the second highest cause of morbidity and mortality worldwide while also impacting the world economy, triggering substantial financial burden in national health systems. High levels of blood glucose, homocysteine, and cholesterol are causative factors for atherothrombosis. These molecules induce erythrocyte dysfunction, which can culminate in atherosclerosis, thrombosis, thrombus stabilization, and post-stroke hypoxia. Glucose, toxic lipids, and homocysteine result in erythrocyte oxidative stress. This leads to phosphatidylserine exposure, promoting phagocytosis. Phagocytosis by endothelial cells, intraplaque macrophages, and vascular smooth muscle cells contribute to the expansion of the atherosclerotic plaque. In addition, oxidative stress-induced erythrocytes and endothelial cell arginase upregulation limit the pool for nitric oxide synthesis, leading to endothelial activation. Increased arginase activity may also lead to the formation of polyamines, which limit the deformability of red blood cells, hence facilitating erythrophagocytosis. Erythrocytes can also participate in the activation of platelets through the release of ADP and ATP and the activation of death receptors and pro-thrombin. Damaged erythrocytes can also associate with neutrophil extracellular traps and subsequently activate T lymphocytes. In addition, reduced levels of CD47 protein in the surface of red blood cells can also lead to erythrophagocytosis and a reduced association with fibrinogen. In the ischemic tissue, impaired erythrocyte 2,3 biphosphoglycerate, because of obesity or aging, can also favor hypoxic brain inflammation, while the release of damage molecules can lead to further erythrocyte dysfunction and death.

Cirrhosis-induced oxidative stress in erythrocytes: The therapeutic potential of taurine.

Cholestasis/cirrhosis could induce erythrocyte lysis. The incidence of various types of anemia in cirrhosis is approx. 75%. Several studies have mentioned the pivotal role of oxidative stress in this complication. Taurine (TAU) is the human body's most abundant free amino acid. TAU is known as a robust cell membrane stabilizer. Many studies have mentioned that TAU could counteract oxidative stress in various experimental models. The current study was intended to evaluate the effect of TAU on erythrocytes in cirrhotic rats. Bile duct ligation (BDL) surgery was carried out on rats. Then, complete blood count (CBC), hemoglobin (Hgb), hematocrit (HTC), and erythrocytes' G6PD, catalase (CAT), and superoxide dismutase (SOD) activity were measured. Moreover, biomarkers of oxidative stress were assessed, and the erythrocytes' morphological changes were monitored in the cirrhotic mice exposed to TAU (0.25%, 0.5%, and 1% w : v in drinking water). Significant changes in the assessed erythrocyte parameters (G6PD activity, Hgb, HTC, and erythrocyte count) and red blood cells (RBC) morphological alterations were detected on day 42 after BDL surgery. Biomarkers of oxidative stress also did not change at the time points, except on post-BDL days 28 and 42. A significant decrease in blood parameters was evident at post-BDL day 42. All doses of TAU (0.25%, 0.5%, and 1% w : v in drinking water) significantly improved erythrocyte parameters and encountered oxidative stress in the erythrocytes of cirrhotic animals. These data indicate that TAU could be a safe agent to mitigate cirrhosis-induced erythrocyte damage and anemia. Further investigations are necessary to prove this in clinical settings.

COVID-19 Infection Changes the Functions and Morphology of Erythrocytes: A Multidisciplinary Study

Hematological problems are associated with Coronavirus disease 2019 (COVID-19). Respiratory impairment is the higher point studied, although without experimental studies related to the oxygen transport performed by erythrocytes. Therefore, we decided to investigate if erythrocytes from COVID-19 patients have their functionality changed. The case-control study included hospitalized patients with a positive real-time polymerase chain reaction (RT-PCR) result admitted to University Hospital. Volunteers (negative RT-PCR results) were recruited as a control group. Thus, we assessed different erythrocytes parameters, oxidative stress markers, and biophysical studies using whole blood and isolated hemoglobin. We found a decrease of 51% in oxygen uptake and reduced antioxidant enzyme activity in COVID-19 patients compared to controls. Raman spectrometry showed structural changes in the hemoglobin and lipids of the erythrocytes from COVID-19 patients; thus, these results were consolidated with an increase in Young’s modulus in erythrocytes followed by morphology changes. Besides, isolated hemoglobin from COVID-19 patients has a distinct interaction profile using a ligand model compared to the control. COVID-19 leads to structural, functional, and morphological damage to human erythrocytes. Our data showed structural and molecular changes and induction of oxidative stress in erythrocytes by COVID-19, a new perspective on the contribution of erythrocytes to a respiratory commitment in COVID-19.

OXIDATIVE METABOLISM OF ERYTHROCYTES IN PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA AND ITS SIGNIFICANCE IN DIAGNOSIS AND PROGNOSIS OF THE DISEASE

Community-acquired pneumonia is remaining one of the most common diseases in the world. The high morbidity and mortality rates establish the necessity for further in-depth research into the mechanisms of the development and progression of the disease, finding ways to optimize diagnosis and treatment. The purpose of this study is to investigate indicators of the oxidative metabolism of erythrocytes in patients with community-acquired pneumonia and to evaluate its significance in the pathogenesis of the disease. Participants and methods: the study involved 20 adult patients suffering from community-acquired pneumonia, who took the course of treatment at the therapeutic department of the City Clinical Hospital No. 25, Kharkiv. The diagnosis of community-acquired pneumonia was established on the basis of epidemiological, clinical, laboratory, and radiological findings. All indicators were compared with the findings in the group of healthy individuals. A comparative analysis of the content of carbonyl derivatives, the level of malondialdehyde, and membrane-bound haemoglobin was carried out. We revealed the presence of intracellular oxidative stress in erythrocytes of the patients with community-acquired pneumonia that leads to damage to their membranes and the release of hemoglobin into the blood plasma. Conclusion. Oxidative metabolism provokes an impairment of redox reactions in the blood plasma and contributes to the progression of the disease. Hypoxia, which develops during community-acquired pneumonia, aggravates the course of the disease and worsens the prognosis for recovery. The obtained results allow us to recommend the addition of antihypoxic agents to the traditional antibacterial therapy of community-acquired pneumonia.

Effects of N-acetylcysteine and dexamethasone on the antioxidant status of erythrocytes in experimental immunogenic uveitis

Objective . To study the effect of N-acetylcysteine (NAC) and dexamethasone over the parameters of lipid peroxidation (LPO) and antioxidant defence (AOD) in erythrocytes of rabbits with experimental immunogenic uveitis (EIU). Materials and methods . An experimental study was carried out on 45 rabbits. Animals with EIU were treated with placebo, NAC, dexamethasone, or a combination of NAC and dexamethasone. Parameters of lipid peroxidation (diene conjugates, triene conjugates, malondialdehyde) and AOD (catalase activity, reduced glutathione, oxidized glutathione and their ratio, superoxide dismutase) were observed in blood erythrocytes of rabits. Results . EIU in rabbits was accompanied by a significant elevation of LPO parameters and inhibition of AOD in erythrocytes. NAC significantly reduced the intensity of oxidative stress in erythrocytes, and also increased the AOP parameters, including the content of reduced glutathione. Dexamethasone led to the inhibition of the glutathione system. The combined application of NAC and dexamethasone revealed the synergism of their pharmacological action. Conclusion . EIU in rabbits is accompanied by systemic manifestations of oxidative stress. NAC has a pronounced antioxidant effect on the redox status of blood erythrocytes. Dexamethasone has an inhibitory effect on the glutathione system. The combined parenteral administration of NAC and dexamethasone revealed their combined synergistic pharmacological effect.

The Nutraceuticals as Modern Key to Achieve Erythrocyte Oxidative Stress Fighting in Osteoarthritis.

Osteoarthritis (OA), the most common joint disease, shows an increasing prevalence in the aging population in industrialized countries. OA is characterized by low-grade chronic inflammation, which causes degeneration of all joint tissues, such as articular cartilage, subchondral bone, and synovial membrane, leading to pain and loss of functionality. Erythrocytes, the most abundant blood cells, have as their primary function oxygen transport, which induces reactive oxygen species (ROS) production. For this reason, the erythrocytes have several mechanisms to counteract ROS injuries, which cause damage to lipids and proteins of the cell membrane. Oxidative stress and inflammation are highly correlated and are both causes of joint disorders. In the synovial fluid and blood of osteoarthritis patients, erythrocyte antioxidant enzyme expression is decreased. To date, OA is a non-curable disease, treated mainly with non-steroidal anti-inflammatory drugs and corticosteroids for a prolonged period of time, which cause several side effects; thus, the search for natural remedies with anti-inflammatory and antioxidant activities is always ongoing. In this review, we analyze several manuscripts describing the effect of traditional remedies, such as Harpagophytum procumbens, Curcumin longa, and Boswellia serrata extracts, in the treatments of OA for their anti-inflammatory, analgesic, and antioxidant activity. The effects of such remedies have been studied both in in vitro and in vivo models, considering both joint cells and erythrocytes.

Missense mutation in RPS7 causes Diamond-Blackfan anemia via alteration of erythrocyte metabolism, protein translation and induction of ribosomal stress

Diamond-Blackfan anemia (DBA) is predominantly underlined by mutations in genes encoding ribosomal proteins (RP); however, its etiology remains unexplained in approximately 25 % of patients.We previously reported a novel heterozygous RPS7 mutation hg38 chr2:g.3,580,153G > T p.V134F in one female patient and two asymptomatic family members, in whom mild anemia and increased erythrocyte adenosine deaminase (eADA) activity were detected. We observed that altered erythrocyte metabolism and oxidative stress which may negatively affect the lifespan of erythrocytes distinguishes the patient from her asymptomatic family members. Pathogenicity of the RPS7 p.V134F mutation was extensively validated including molecular defects in protein translational activity and ribosomal stress activation in the cellular model of this variant.

Myostatin Knockout Limits Exercise-Induced Reduction in Bovine Erythrocyte Oxidative Stress by Enhancing the Efficiency of the Pentose Phosphate Pathway.

Simple SummaryMyostatin (MSTN) is mainly expressed in skeletal muscle and is involved in the regulation of skeletal muscle growth and development. Loss of MSTN results in muscle hypertrophy. In this study; red blood cells were used as materials to study the effect of MSTN on the antioxidant capacity of bovine erythrocyte after exhaustive exercise. The findings suggest that knockdown of MSTN accelerates the pentose phosphate pathway; thereby enhancing the antioxidant capacity of erythrocytes.Moderate exercise can strengthen the body, however, exhaustive exercise generates large amounts of reactive oxygen species (ROS). Although erythrocytes have antioxidant systems that quickly eliminate ROS, erythrocytes become overwhelmed by ROS when the body is under oxidative stress, such as during exhaustive exercise. Myostatin (MSTN) has important effects on muscle hair development. Individuals lacking myostatin (MSTN) exhibit increased muscle mass. The purpose of this study was to investigate the mechanism by which MSTN affects erythrocyte antioxidant changes after exhaustive exercise in cattle. Antioxidant and metabolite detection analysis, western blotting, immunofluorescence, and fatty acid methyl ester analysis were used to assess exercise-associated antioxidant changes in erythrocytes with or without MSTN. Knockdown of MSTN enhances Glucose-6-phosphate dehydrogenase (G6PD) activity after exhaustive exercise. MSTN and its receptors were present on the erythrocyte membrane, but their levels, especially that of TGF-β RI, were significantly reduced in the absence of MSTN and following exhaustive exercise. Our results suggest that knockout of MSTN accelerates the pentose phosphate pathway (PPP), thereby enhancing the antioxidant capacity of erythrocytes. These results provide important insights into the role of MSTN in erythrocyte antioxidant regulation after exhaustive exercise.

Mitapivat increases ATP and decreases oxidative stress and erythrocyte mitochondria retention in a SCD mouse model

Polymerization of deoxygenated sickle hemoglobin (HbS) leads to erythrocyte sickling. Enhancing activity of the erythrocyte glycolytic pathway has anti-sickling potential as this reduces 2,3-diphosphoglycerate (2,3-DPG) and increases ATP, factors that decrease HbS polymerization and improve erythrocyte membrane integrity. These factors can be modulated by mitapivat, which activates erythrocyte pyruvate kinase (PKR) and improves sickling kinetics in SCD patients. We investigated mechanisms by which mitapivat may impact SCD by examining its effects in the Townes SCD mouse model. Control (HbAA) and sickle (HbSS) mice were treated with mitapivat or vehicle. Surprisingly, HbSS had higher PKR protein, higher ATP, and lower 2,3-DPG levels, compared to HbAA mice, in contrast with humans with SCD, in whom 2,3-DPG is elevated compared to healthy subjects. Despite our inability to investigate 2,3-DPG-mediated sickling and hemoglobin effects, mitapivat yielded potential benefits in HbSS mice. Mitapivat further increased ATP without significantly changing 2,3-DPG or hemoglobin levels, and decreased levels of leukocytosis, erythrocyte oxidative stress, and the percentage of erythrocytes that retained mitochondria in HbSS mice. These data suggest that, even though Townes HbSS mice have increased PKR activity, further activation of PKR with mitapivat yields potentially beneficial effects that are independent of changes in sickling or hemoglobin levels.

Animal Biomonitoring for the Surveillance of Environment Affected by the Presence of Slight Contamination by β-HCH.

The aim of this study was to evaluate the influence of hidden environmental pollution on some blood parameters of sheep to detect susceptible biomarkers able to reveal slight contamination. Four dairy sheep farms, two with semi-extensive and two with intensive type systems were involved in this study. Two farms in different systems were chosen as properly located in a southern area of Latium (Italy), close to the Sacco River, in which contamination with β-hexachlorocyclohexane (β-HCH) occurred in the past due to industrial waste. A recent study established the presence of low but detectable residual contamination in these areas. The other two farms were outside the contaminated area. Erythrocyte glutathione transferase (e-GST) and oxidative stress parameters were monitored as well as some immune response and metabolic profile parameters throughout the investigated period of four months. The present study showed a relevant and significant increase in e-GST (+63%) in the extensive farming system of the contaminated area, whereas some immune response biomarkers, i.e., white blood cells, neutrophils, lymphocytes, and lysozyme resulted within the physiological range. In all farms, oxidative stress and acute phase response parameters were also within the physiological range. Our results suggest that e-GST is a very effective alarm signal to reveal “hidden” persistent contamination by β-HCH, and reasonably, by many other different dangerous pollutants.

Erythrocyte oxidative stress and thrombosis.

Thrombosis is a common disorder with a relevant burden of morbidity and mortality worldwide, particularly among elderly patients. Growing evidence demonstrated a direct role of oxidative stress in thrombosis, with various cell types contributing to this process. Among them, erythrocytes produce high quantities of intracellular reactive oxygen species (ROS) by NADPH oxidase activation and haemoglobin autoxidation. Concomitantly, extracellular ROS released by other cells in the blood flow can be uptaken and accumulate within erythrocytes. This oxidative milieu can alter erythrocyte membrane structure, leading to an impaired erythrocyte function, and promoting erythrocytes lysis, binding to endothelial cells, activation of platelet and of coagulation factors, phosphatidylserine exposure and release of microvesicles. Moreover, these abnormal erythrocytes are able to adhere to the vessel wall, contributing to thrombin generation within the thrombus. This process results in accelerated haemolysis and in a hypercoagulable state, in which structurally impaired erythrocytes contribute to increase thrombus size, to reduce its permeability and susceptibility to lysis. However, the wide plethora of mechanisms by which oxidised erythrocytes contribute to thrombosis is not completely elucidated. This review discusses the main biochemical aspects linking erythrocytes, oxidative stress and thrombosis, addressing their potential implication for clinical and therapeutic management.