scholarly journals Oxidative Stress in Multiple Organ Damage in Hypertension, Diabetes and CKD, Mechanisms and New Therapeutic Possibilities

10.5772/33448 ◽  
2012 ◽  
Author(s):  
Tatsuo Shimosawa ◽  
Tomoyo Kaneko ◽  
Xu Qingyou ◽  
Yusei Miyamoto ◽  
Mu Shengyu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Organ Damage ◽  
Multiple Organ ◽  
Therapeutic Possibilities

scholarly journals THE CHANGES IN DYNAMICS OF ORNITHINE CYCLE COMPONENTS LEVELS DURING THE ACUTE PERIOD OF POLYTRAUMA

2019 ◽  
Vol 72 (9) ◽  
pp. 1781-1785
Author(s):  
Nataliya Matolinets
Keyword(s):  
Oxidative Stress ◽  
Intensive Care ◽  
Serum Levels ◽  
Organ Damage ◽  
Multiple Organ ◽  
Oxidation Products ◽  
Acute Period ◽  
Proinflammatory Mediators ◽  
Biomechanical Parameters ◽  
Injury Causes

Introduction: Polytrauma or multiple organ damage is associated with shock and lead to systemic inflammation, oxidative stress and endothelial dysfunction. A severe mechanical injury causes an increased proinflammatory mediators and cytokines levels. Among them, the overproduction of nitric oxide and its oxidation products play a key role in tissue damage. The aim: To evaluate the changes in dynamics of some ornithine cycle components levels during acute period of polytrauma. Materials and methods: We measured standard biomechanical parameters and serum levels of NO, sum of nitrite and nitrate (NOx), L-arginine, arginase, and peroxynitrite. According to the ISS, the study included patients with moderate (n=15) to severe (n=15) polytrauma. Results: In 24 hours after polytrauma on the background of intensive care, it was observed significant increasing of NO, NOx, and arginase levels (severe cases) with decreasing of L-arginine and peroxynitrite levels. Conclusions: Elevated NO and NOx serum levels in patients with polytrauma is associated with increasing of arginase activity with decreasing of L-arginine and peroxynitrite levels on the background of intensive care.

Reduced Oxidative Stress and Enhanced Nitric Oxide (NO) Bioavailability in Transgenic-Knockout Sickle Mice Expressing Fetal Hemoglobin (HbF) Is Mediated by Decreased Sickling and Hemolysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 842-842
Author(s):  
Trisha Dasgupta ◽  
Mary E. Fabry ◽  
Dhananjay K. Kaul
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Genetic Manipulation ◽  
Fetal Hemoglobin ◽  
Organ Damage ◽  
Multiple Organ ◽  
Protective Effects ◽  
Cell Disease ◽  
No Bioavailability

Abstract The primary event in the vaso-occlusive pathophysiology of sickle cell disease (SCD) is polymerization of hemoglobin S under deoxygenated conditions. In SCD, sub-clinical transient vaso-occlusive events caused by red cell sickling are likely to be more frequent resulting in “reperfusion injury” that generates reactive oxygen species and results in chronic oxidative stress that will contribute to multiple organ damage. In fact, previous studies have suggested that sickling is etiologic to repefusion injury and oxidative stress (Kaul and Hebbel, JCI, 2000), although the effect of antisickling therapy on oxidative stress has not been evaluated. Increasing the levels of antisickling fetal hemoglobin (HbF) by hydroxyurea therapy markedly reduces polymer formation. HbF exerts an ameliorating effect in sickle cell disease patients both on red cells and in the prevention of multiple organ damage. Here, we hypothesize that induction of HbF by genetic manipulation (in the absence of pharmacological manipulation) will reduce organ oxidative stress by reducing sickling and hemolysis, and thereby increase NO bioavailability. To test our hypothesis, we measured activity of selected antioxidants and lipid peroxidation (LPO) in BERK mice expressing exclusively human α- and βS-globins and varying levels of HbF, i.e., BERK (<1% HbF), BERKγM (20% HbF) and BERKγH (40% HbF). Percent sickled cells in venous samples (drawn in 2.5% glutaraldehyde solution in 0.1M cacodylate buffer) showed a distinct decrease with increased %HbF (P<0.05, multiple comparisons). Consistent with maximal sickling, BERK mice showed 5.4–6.9-fold increase in LPO in various tissues (muscle, kidney and liver) compared with C57BL controls (P<0.001). In contrast, BERKγM and BERKγH mice showed a marked decrease (73% and 80%, respectively) in LPO compared with BERK mice (P<0.001). Also, activity/levels of antioxidants (superoxide dismutase [SOD], catalase, glutathione peroxidase [GPx] and reduced glutathione [GSH]) showed significant decreases in BERK mice (P<0.001–0.00001). On the other hand, BERKγM and BERKγH mice showed significant increases in antioxidant activity (P<0.05–0.0001). Induction of HbF was associated with increased levels of NO metabolites (NOx) and reduced hemolysis; the latter is in agreement with our previous observations in BERKγM mice (Kaul et al. JCI, 2004). These results strongly suggest that reduced sickling and hemolysis in the presence of HbF cause increased NO bioavailability. NO is well known to exert antioxidative effects. Thus, we show for the first time that the induction of antisickling HbF leads to an increase in NO bioavailability and a decrease in oxidative stress, and that these protective effects are mediated primarily by reduced intravascular sickling.

scholarly journals Antisickling property of fetal hemoglobin enhances nitric oxide bioavailability and ameliorates organ oxidative stress in transgenic-knockout sickle mice

2010 ◽  
Vol 298 (2) ◽  
pp. R394-R402 ◽  
Author(s):  
Trisha Dasgupta ◽  
Mary E. Fabry ◽  
Dhananjay K. Kaul
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Genetic Manipulation ◽  
Fetal Hemoglobin ◽  
Inverse Correlation ◽  
Organ Damage ◽  
Multiple Organ ◽  
Activity Levels ◽  
No Bioavailability ◽  
And Oxidative Stress

In sickle cell disease (SCD), the events originating from hemoglobin S polymerization and intravascular sickling lead to reperfusion injury, hemolysis, decreased nitric oxide (NO) bioavailability, and oxidative stress. Oxidative stress is implicated as a contributing factor to multiple organ damage in SCD. We hypothesize that inhibition of sickling by genetic manipulation to enhance antisickling fetal hemoglobin (HbF) expression will have an ameliorating effect on oxidative stress by decreasing intravascular sickling and hemolysis and enhancing NO bioavailability. We tested this hypothesis in BERK (Berkeley) mice expressing exclusively human α- and βS-globins and varying levels of HbF, i.e., BERK (<1% HbF), BERKγM (20% HbF) and BERKγH (40% HbF). Intravascular sickling showed a distinct decrease with increased expression of HbF, which was accompanied by decreased hemolysis and increased NO metabolites (NOx) levels. Consistent with decreased intravascular sickling and increased NO bioavailability, BERKγM and BERKγH mice showed markedly decreased lipid peroxidation accompanied by increased activity/levels of antioxidants [superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and reduced glutathione (GSH)] in the muscle, kidney, and liver compared with BERK mice ( P < 0.05–0.0001). NOxlevels showed a strong inverse correlation with hemolytic rate and oxidative stress. Decreased oxidative stress in the presence of elevated HbF levels led to an anti-inflammatory effect as evidenced by decreased peripheral leukocyte counts. These results show that the protective effect of HbF is mediated primarily by decreasing intravascular sickling resulting in decreased oxidative stress and increased NO bioavailability.

scholarly journals Protective Effects of GYY4137 on Renal Ischaemia/Reperfusion Injury through Nrf2-Mediated Antioxidant Defence

2021 ◽  
pp. 1-9
Author(s):  
Hongmei Zhao ◽  
Yun Qiu ◽  
Yichen Wu ◽  
Hong Sun ◽  
Sumin Gao
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Nuclear Translocation ◽  
Organ Damage ◽  
Related Factor ◽  
Protective Effects ◽  
Ischaemia Reperfusion Injury ◽  
Renal Ischaemia ◽  
Ischaemia Reperfusion ◽  
Renal Histology

<b><i>Introduction/Aims:</i></b> Hydrogen sulfide (H<sub>2</sub>S) is considered to be the third most important endogenous gasotransmitter in organisms. GYY4137 is a long-acting donor for H<sub>2</sub>S, a gas transmitter that has been shown to prevent multi-organ damage in animal studies. We previously reported the effect of GYY4137 on cardiac ischaemia reperfusion injury (IRI) in diabetic mice. However, the role and mechanism of GYY4137 in renal IRI are poorly understood. The aims of this study were to determine whether GYY4137 can effectively alleviate the injury induced by renal ischaemia reperfusion and to explore its possible mechanism. <b><i>Methods:</i></b> Mice received right nephrectomy and clipping of the left renal pedicle for 45 min. GYY4137 was administered by intraperitoneal injection for 2 consecutive days before the operation. The model of hypoxia/reoxygenation injury was established in HK-2 cells, which were pre-treated with or without GYY4137. Renal histology, function, apoptosis, and oxidative stress were measured. Western blot was used to measure the target ­protein after renal IRI. <b><i>Results:</i></b> The results indicated that GYY4137 had a clear protective effect on renal IRI as reflected by the attenuation of renal dysfunction, renal tubule injury, and apoptosis. Moreover, GYY4137 remarkably reduced renal IRI-induced oxidative stress. GYY4137 significantly elevated the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2) and the expression of antioxidant enzymes regulated by Nrf2, including SOD, HO-1, and NQO-1. <b><i>Conclusions:</i></b> GYY4137 alleviates ischaemia reperfusion-induced renal injury through activating the antioxidant effect mediated by Nrf2 signalling.

scholarly journals Role of combining anticoagulant and antiplatelet agents in COVID-19 treatment: a rapid review

Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001628
Author(s):  
Kamal Matli ◽  
Raymond Farah ◽  
Mario Maalouf ◽  
Nibal Chamoun ◽  
Christy Costanian ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Anticoagulation Therapy ◽  
Antiplatelet Agents ◽  
Organ Damage ◽  
Multiple Organ ◽  
Rapid Review ◽  
Thromboembolic Events ◽  
Antithrombotic Agent ◽  
Heparin Resistance

Although primarily affecting the respiratory system, COVID-19 causes multiple organ damage. One of its grave consequences is a prothrombotic state that manifests as thrombotic, microthrombotic and thromboembolic events. Therefore, understanding the effect of antiplatelet and anticoagulation therapy in the context of COVID-19 treatment is important. The aim of this rapid review was to highlight the role of thrombosis in COVID-19 and to provide new insights on the use of antithrombotic therapy in its management. A rapid systematic review was performed using preferred reporting items for systematic reviews. Papers published in English on antithrombotic agent use and COVID-19 complications were eligible. Results showed that the use of anticoagulants increased survival and reduced thromboembolic events in patients. However, despite the use of anticoagulants, patients still suffered thrombotic events likely due to heparin resistance. Data on antiplatelet use in combination with anticoagulants in the setting of COVID-19 are quite scarce. Current side effects of anticoagulation therapy emphasise the need to update treatment guidelines. In this rapid review, we address a possible modulatory role of antiplatelet and anticoagulant combination against COVID-19 pathogenesis. This combination may be an effective form of adjuvant therapy against COVID-19 infection. However, further studies are needed to elucidate potential risks and benefits associated with this combination.

scholarly journals Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 936
Author(s):  
Chien-Lin Lu ◽  
Cai-Mei Zheng ◽  
Kuo-Cheng Lu ◽  
Min-Tser Liao ◽  
Kun-Lin Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Wasting ◽  
Mesangial Cells ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Tubulointerstitial Injury

The accumulation of the uremic toxin indoxyl sulfate (IS) induces target organ damage in chronic kidney disease (CKD) patients, and causes complications including cardiovascular diseases, renal osteodystrophy, muscle wasting, and anemia. IS stimulates reactive oxygen species (ROS) production in CKD, which impairs glomerular filtration by a direct cytotoxic effect on the mesangial cells. IS further reduces antioxidant capacity in renal proximal tubular cells and contributes to tubulointerstitial injury. IS-induced ROS formation triggers the switching of vascular smooth muscular cells to the osteoblastic phenotype, which induces cardiovascular risk. Low-turnover bone disease seen in early CKD relies on the inhibitory effects of IS on osteoblast viability and differentiation, and osteoblastic signaling via the parathyroid hormone. Excessive ROS and inflammatory cytokine releases caused by IS directly inhibit myocyte growth in muscle wasting via myokines’ effects. Moreover, IS triggers eryptosis via ROS-mediated oxidative stress, and elevates hepcidin levels in order to prevent iron flux in circulation in renal anemia. Thus, IS-induced oxidative stress underlies the mechanisms in CKD-related complications. This review summarizes the underlying mechanisms of how IS mediates oxidative stress in the pathogenesis of CKD’s complications. Furthermore, we also discuss the potential role of oral AST-120 in attenuating IS-mediated oxidative stress after gastrointestinal adsorption of the IS precursor indole.

scholarly journals Sickle Cell Disease: Role of Oxidative Stress and Antioxidant Therapy

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 296
Author(s):  
Rosa Vona ◽  
Nadia Maria Sposi ◽  
Lorenza Mattia ◽  
Lucrezia Gambardella ◽  
Elisabetta Straface ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Globin Gene ◽  
Organ Damage ◽  
Cell Disease ◽  
Vessel Occlusion ◽  
Antioxidant Agents ◽  
Oxidant Status

Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb), which affects approximately a million people worldwide. It is characterized by a single nucleotide substitution in the β-globin gene, leading to the production of abnormal sickle hemoglobin (HbS) with multi-system consequences. HbS polymerization is the primary event in SCD. Repeated polymerization and depolymerization of Hb causes oxidative stress that plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e., by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population.

Cancer and COVID-19: A proposed mechanism with therapeutic interventions.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3135-3135
Author(s):  
Yan Leyfman ◽  
Nancy Emmanuel ◽  
Aleksey Tentler ◽  
Jared Cappelli ◽  
Timothy K Erick ◽  
...  
Keyword(s):  
Respiratory Illness ◽  
Organ Damage ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Actual Number ◽  
Data Registry ◽  
Number Of Patients ◽  
Increased Risk ◽  
Life Threatening ◽  
Active Cancer

3135 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that causes the respiratory illness coronavirus disease 2019 (COVID-19). COVID-19 ranges in severity from an asymptomatic viral infection to life-threatening cases of pneumonia, acute respiratory distress syndrome (ARDS), multi-organ damage and sepsis. Cancer patients are at an increased risk of severe SARS-CoV-2 infection due to their immunocompromised status. We propose a mechanism by which SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation and hypoxia-induced cellular metabolic alterations leading to cell death. Hypoxia is also induced by malignancy due to alterations in metabolism, resulting in greater IL-6 secretion. Methods: To highlight the possible effect of active cancer on the likelihood of hypoxia in COVID-19, we analyzed the correlation between cancer status and the severity of COVID-19 from the COVID-19 and Cancer Consortium data registry. For cancer status, we looked at progressive cancer and remission of cancer only -- those being the two extremes of presence and absence of uncontrolled cancer. Similar to prior studies, the severity of COVID-19 was used as an indication of hypoxia. Results: We observed a 24% positive deviation between expected and actual number of patients with actively progressing cancer who had hypoxic COVID-19 (moderate to severe), and a 26.9% negative deviation between expected and actual number of patients with active cancer who had no hypoxia with COVID-19 (p<0.0001). Conversely, for patients with cancer in remission, there was only a +5.8% and -5.1% deviation between expected and actual number of patients who did not have hypoxia and who had hypoxia, respectively. Conclusions: These results suggest that in the presence of poorly controlled malignancy, there is an increased likelihood of hypoxia in patients with COVID-19, thereby exacerbating downstream cytokine release syndrome and contributing to prolonged systemic inflammatory injury. Appreciating this pathway, future therapies can be developed to target the pathogenesis of both diseases and prevent progression, as seen with mesenchymal stem cells, which demonstrated a 91% overall survival and 100% survival in patients younger than 85 years old at one month after a single treatment.[Table: see text]

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