Oxidative and Nitrosative Stress in the Pathogenesis of Obstructive Lung Diseases of Increasing Severity

2020 ◽  
Vol 27 (42) ◽  
pp. 7149-7158
Author(s):  
Antonino Di Stefano ◽  
Mauro Maniscalco ◽  
Bruno Balbi ◽  
Fabio L.M. Ricciardolo
Keyword(s):  
Oxidative Stress ◽  
Lung Diseases ◽  
Nitrosative Stress ◽  
Cell Damage ◽  
Severe Disease ◽  
Protein Nitration ◽  
Phagocytic Cells ◽  
Oxidative And Nitrosative Stress ◽  
Obstructive Lung Diseases ◽  
Copd Patients

The imbalance between increased oxidative agents and antioxidant defence mechanisms is central in the pathogenesis of obstructive lung diseases such as asthma and COPD. In these patients, there are increased levels of reactive oxygen species. Superoxide anions (O<sub>2</sub> -), Hydrogen Peroxide (H<sub>2</sub>O<sub>2</sub>) and hydroxyl radicals (•OH) are critical for the formation of further cytotoxic radicals in the bronchi and lung parenchyma. Chronic inflammation, partly induced by oxidative stress, can further increase the oxidant burden through activated phagocytic cells (neutrophils, eosinophils, macrophages), particularly in severer disease states. Antioxidants and anti-inflammatory genes are, in fact, frequently downregulated in diseased patients. Nrf2, which activates the Antioxidant Response Element (ARE) leading to upregulation of GPx, thiol metabolism-associated detoxifying enzymes (GSTs) and stressresponse genes (HO-1) are all downregulated in animal models and patients with asthma and COPD. An exaggerated production of Nitric Oxide (NO) in the presence of oxidative stress can promote the formation of oxidizing reactive nitrogen species, such as peroxynitrite (ONO<sub>2</sub> -), leading to nitration and DNA damage, inhibition of mitochondrial respiration, protein dysfunction, and cell damage in the biological systems. Protein nitration also occurs by activation of myeloperoxidase and H<sub>2</sub>O<sub>2</sub>, promoting oxidation of nitrite (NO<sub>2</sub> -). There is increased nitrotyrosine and myeloperoxidase in the bronchi of COPD patients, particularly in severe disease. The decreased peroxynitrite inhibitory activity found in induced sputum of COPD patients correlates with pulmonary function. Markers of protein nitration - 3- nitrotyrosine, 3-bromotyrosine, and 3-chlorotyrosine - are increased in the bronchoalveolar lavage of severe asthmatics. Targeting the oxidative, nitrosative stress and associated lung inflammation through the use of either denitration mechanisms or new drug delivery strategies for antioxidant administration could improve the treatment of these chronic disabling obstructive lung diseases.

scholarly journals Centaurium erythraea extract reduces redox imbalance and improves insulin expression and secretion in pancreatic β-cells exposed to oxidative and nitrosative stress

2020 ◽  
Vol 72 (1) ◽  
pp. 117-128
Author(s):  
Milos Djordjevic ◽  
Nevena Grdovic ◽  
Mirjana Mihailovic ◽  
Jelena Arambasic-Jovanovic ◽  
Aleksandra Uskokovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitrosative Stress ◽  
Cell Damage ◽  
Redox Homeostasis ◽  
Protein S ◽  
Oxidative And Nitrosative Stress ◽  
Protein Levels ◽  
Insulin Expression ◽  
Redox Active ◽  
Centaurium Erythraea

Oxidative stress is one of the major mechanisms that underlies the damage of pancreatic ?-cells and defects in insulin secretion in diabetes. As herbal preparations can alleviate oxidative stress through their redox-active secondary metabolites, in this study we investigated the cytoprotective effects of Centaurium erythraea extract (CEe) against H2O2- and SNP-induced oxidative/nitrosative stress in Rin-5F ?-cells. The antioxidant activity of CEe and its effect on cell survival and insulin expression/secretion were evaluated. The CEe increased cell viability and ameliorated the disturbance of redox homeostasis in H2O2- and SNP-treated cells by decreasing DNA damage, lipid peroxidation and protein S-glutathionylation. The CEe restored GSH homeostasis in H2O2-treated ?-cells and attenuated the SNP-induced disturbance of the GSH/ GSSG ratio. The H2O2- and SNP-induced disruption of CAT, GPx, GR, MnSOD and CuZnSOD activities was adjusted by the CEe towards control values, as well as mRNA and protein levels of GPx, MnSOD and CAT. The CEe increased insulin expression/secretion particularly in H2O2-treated ?-cells, which was in accordance with the more pronounced antioxidant effect of the CEe observed in H2O2-treated ?-cells as compared to SNP-treated cells. These findings support the beneficial effect of the CEe in preventing or slowing down ?-cell damage and dysfunction caused by oxidative/nitrosative stress during diabetes development.

scholarly journals Myeloperoxidase-Related Chlorination Activity Is Positively Associated with Circulating Ceruloplasmin in Chronic Heart Failure Patients: Relationship with Neurohormonal, Inflammatory, and Nutritional Parameters

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Aderville Cabassi ◽  
Simone Maurizio Binno ◽  
Stefano Tedeschi ◽  
Gallia Graiani ◽  
Cinzia Galizia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Nitrosative Stress ◽  
Defense Mechanism ◽  
Nyha Class ◽  
Protein Nitration ◽  
Class Iii ◽  
Oxidative And Nitrosative Stress ◽  
Radical Production ◽  
Antioxidant Function ◽  
The Relationship

Rationale. Heart failure (HF) is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. Both chlorinating and peroxidase cycle of Myeloperoxidase (MPO) contribute to oxidative and nitrosative stress and are involved in tyrosine nitration of protein. Ceruloplasmin (Cp) has antioxidant function through its ferroxidase I (FeOxI) activity and has recently been proposed as a physiological defense mechanism against MPO inappropriate actions.Objective. We investigated the relationship between plasma MPO-related chlorinating activity, Cp and FeOxI, and nitrosative stress, inflammatory, neurohormonal, and nutritional biomarkers in HF patients.Methods and Results. In chronic HF patients (n=81, 76±9 years, NYHA Class II (26); Class III (29); Class IV (26)) and age-matched controls (n=17, 75±11 years, CTR), plasma MPO chlorinating activity, Cp, FeOxI, nitrated protein, free Malondialdehyde, BNP, norepinephrine, hsCRP, albumin, and prealbumin were measured. Plasma MPO chlorinating activity, Cp, BNP, norepinephrine, and hsCRP were increased in HF versus CTR. FeOxI, albumin, and prealbumin were decreased in HF. MPO-related chlorinating activity was positively related to Cp (r= 0.363,P<0.001), nitrated protein, hsCRP, and BNP and inversely to albumin.Conclusions. Plasma MPO chlorinated activity is increased in elderly chronic HF patients and positively associated with Cp, inflammatory, neurohormonal, and nitrosative parameters suggesting a role in HF progression.

scholarly journals The role of oxidative and nitrosative stress in the pathology of osteoarthritis: Novel candidate biomarkers for quantification of degenerative changes in the knee joint

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Alexander Franz ◽  
Laura Joseph ◽  
Constantin Mayer ◽  
Jan-Frieder Harmsen ◽  
Holger Schrumpf ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Synovial Fluid ◽  
Knee Joint ◽  
Human Serum ◽  
Synovial Membrane ◽  
Nitrosative Stress ◽  
Control Groups ◽  
Oxidative And Nitrosative Stress ◽  
And Oxidative Stress

Osteoarthritis (OA) is the most frequently diagnosed joint disorder worldwide with increasing prevalence and crucial impact on the quality of life of affected patients through chronic pain, decreasing mobility and invalidity. Although some risk factors, such as age, obesity and previous joint injury are well established, the exact pathogenesis of OA on a cellular and molecular level remains less understood. Today, the role of nitrosative and oxidative stress has not been investigated conclusively in the pathogenesis of OA yet. Therefore, the objective of this study was to identify biological substances for oxidative and nitrosative stress, which mirror the degenerative processes in an osteoarthritic joint. 69 patients suffering from a diagnosed knee pain participated in this study. Based on the orthopedic diagnosis, patients were classified into an osteoarthritis group (OAG, n=24) or in one of two control groups (meniscopathy, CG1, n=11; anterior cruciate ligament rupture, CG2, n=34). Independently from the study protocol, all patients underwent an invasive surgical intervention which was used to collect samples from the synovial membrane, synovial fluid and human serum. Synovial biopsies were analyzed histopathologically for synovitis (Krenn-Score) and immunohistochemically for detection of end products of oxidative (8-isoprostane F2α) and nitrosative (3-nitrotyrosine) stress. Additionally, the fluid samples were analyzed for 8-isoprostane F2α and 3-nitrotyrosine by competitive ELISA method. The analyzation of inflammation in synovial biopsies revealed a slight synovitis in all three investigated groups. Detectable concentrations of 3-nitrotyrosine were reported in all three investigated groups without showing any significant differences between the synovial biopsies, fluid or human serum. In contrast, significant increased concentrations of 8-isoprostane F2α were detected in OAG compared to both control groups. Furthermore, our data showed a significant correlation between the histopathological synovitis and oxidative stress in OAG (r=0.728, P<0.01). There were no significant differences between the concentrations of 8-isoprostane F2α in synovial fluid and human serum. The findings of the current study support the hypothesis that oxidative and nitrosative stress are components of the multi-factory pathophysiological formation of OA. It seems reasonable that an inflammatory process in the synovial membrane triggers the generation of oxidative and nitrosative acting substances which can lead to a further degradation of the articular cartilage. Based on correlations between the observed degree of inflammation and investigated biomarkers, especially 8-isoprostane F2α seems to be a novel candidate biomarker for OA. However, due to the finding that also both control groups showed increased concentrations of selected biomarkers, future studies have to validate the diagnostic potential of these biomarkers in OA and in related conditions of the knee joint.

scholarly journals Pharmacological and genetic reappraisals of protease and oxidative stress pathways in a mouse model of obstructive lung diseases

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Tsuyoshi Shuto ◽  
Shunsuke Kamei ◽  
Hirofumi Nohara ◽  
Haruka Fujikawa ◽  
Yukihiro Tasaki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Lung Diseases ◽  
Obstructive Lung Diseases ◽  
And Oxidative Stress

scholarly journals Resilience to oxidative and nitrosative stress is mediated by the stressosome, RsbP and SigB inBacillus subtilis.

2018 ◽  
Author(s):  
Vina Tran ◽  
Kara Geraci ◽  
Giovanni Midili ◽  
William Satterwhite ◽  
Rachel Wright ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Environmental Stress ◽  
Nitrosative Stress ◽  
Nutritional Stress ◽  
Cross Protection ◽  
Cross Resistance ◽  
Oxidative And Nitrosative Stress ◽  
General Stress Response ◽  
Energy Stress ◽  
Highly Sensitive

AbstractA bacterium’s ability to thrive in the presence of multiple environmental stressors simultaneously determines its resilience. We showed that activation of the SigB-controlled general stress response by mild environmental or nutritional stress provided significant cross-protection to subsequent lethal oxidative, disulfide and nitrosative stress exposure. SigB activation is mediated via the stressosome and RsbP, the main conduits of environmental and nutritional stress, respectively. Cells exposed to mild environmental stress while lacking the major stressosome components RsbT or RsbRA were highly sensitive to subsequent oxidative stress, whereasrsbRB, rsbRC, rsbRDandytvAnull mutants showed a spectrum of sensitivity, confirming their redundant roles and suggesting they could modulate the signal generated by environmental stress or oxidative stress. Furthermore, from mutant analysis we infer that RsbRA phosphorylation by RsbT was important for this cross-resistance to oxidative stress. By contrast, cells encountering stationary phase stress required RsbP but not RsbT to survive subsequent oxidative stress caused by hydrogen peroxide and diamide. Interestingly, optimum cross-protection against nitrosative stress caused by SNP required SigB but not the known regulators, RsbT and RsbP, suggesting an additional and as yet uncharacterized route of SigB activation independent of the known environmental and energy-stress pathways. Together, these results provide a mechanism for howBacillus subtilispromotes enhanced resistance against lethal oxidative stress during likely physiologically relevant conditions such as mild environmental or nutrient stress.

scholarly journals Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress: Implications for the Pathogenesis of Chronic Chagas Disease Cardiomyopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
João Paulo Silva Nunes ◽  
Pauline Andrieux ◽  
Pauline Brochet ◽  
Rafael Ribeiro Almeida ◽  
Eduardo Kitano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid ◽  
Mitochondrial Dysfunction ◽  
Chagas Disease ◽  
Nitrosative Stress ◽  
Acid Oxidation ◽  
Oxidative And Nitrosative Stress ◽  
Human Cardiomyocytes ◽  
Tnf Α ◽  
Ifn Γ

Infection by the protozoan Trypanosoma cruzi causes Chagas disease cardiomyopathy (CCC) and can lead to arrhythmia, heart failure and death. Chagas disease affects 8 million people worldwide, and chronic production of the cytokines IFN-γ and TNF-α by T cells together with mitochondrial dysfunction are important players for the poor prognosis of the disease. Mitochondria occupy 40% of the cardiomyocytes volume and produce 95% of cellular ATP that sustain the life-long cycles of heart contraction. As IFN-γ and TNF-α have been described to affect mitochondrial function, we hypothesized that IFN-γ and TNF-α are involved in the myocardial mitochondrial dysfunction observed in CCC patients. In this study, we quantified markers of mitochondrial dysfunction and nitro-oxidative stress in CCC heart tissue and in IFN-γ/TNF-α-stimulated AC-16 human cardiomyocytes. We found that CCC myocardium displayed increased levels of nitro-oxidative stress and reduced mitochondrial DNA as compared with myocardial tissue from patients with dilated cardiomyopathy (DCM). IFN-γ/TNF-α treatment of AC-16 cardiomyocytes induced increased nitro-oxidative stress and decreased the mitochondrial membrane potential (ΔΨm). We found that the STAT1/NF-κB/NOS2 axis is involved in the IFN-γ/TNF-α-induced decrease of ΔΨm in AC-16 cardiomyocytes. Furthermore, treatment with mitochondria-sparing agonists of AMPK, NRF2 and SIRT1 rescues ΔΨm in IFN-γ/TNF-α-stimulated cells. Proteomic and gene expression analyses revealed that IFN-γ/TNF-α-treated cells corroborate mitochondrial dysfunction, transmembrane potential of mitochondria, altered fatty acid metabolism and cardiac necrosis/cell death. Functional assays conducted on Seahorse respirometer showed that cytokine-stimulated cells display decreased glycolytic and mitochondrial ATP production, dependency of fatty acid oxidation as well as increased proton leak and non-mitochondrial oxygen consumption. Together, our results suggest that IFN-γ and TNF-α cause direct damage to cardiomyocytes’ mitochondria by promoting oxidative and nitrosative stress and impairing energy production pathways. We hypothesize that treatment with agonists of AMPK, NRF2 and SIRT1 might be an approach to ameliorate the progression of Chagas disease cardiomyopathy.

scholarly journals The Changes of Expression and Methylation of Genes Involved in Oxidative Stress in Course of Chronic Mild Stress and Antidepressant Therapy with Agomelatine

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 644
Author(s):  
Paulina Wigner ◽  
Ewelina Synowiec ◽  
Paweł Jóźwiak ◽  
Piotr Czarny ◽  
Michał Bijak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitrosative Stress ◽  
Mononuclear Cells ◽  
Methylation Status ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Oxidative And Nitrosative Stress ◽  
Peripheral Blood Mononuclear ◽  
Taqman Gene Expression Assay ◽  
The Brain

Preclinical studies conducted so far suggest that oxidative stress processes may be associated with the mechanism of depression development. This study shows the effects of chronic administration of agomelatine on expression and the methylation status of Sod1, Sod2, Gpx1, Gpx4, Cat, Nos1, and Nos2 in the brain stricture and blood in the chronic mild stress (CMS) animal model of depression. The animals were exposed to the CMS procedure and treatment with agomelatine (10 mg/kg/day, IP) for five weeks and then were sacrificed. TaqMan Gene Expression Assay, Western blot, and methylation-sensitive high-resolution melting techniques were used to evaluate mRNA and protein expression of the genes, and the methylation status of their promoters. Gpx1, Gpx4, and Sod2 expression in the PBMCs and Sod1 and Sod2 expression in the brain were reduced in the stressed group after agomelatine administration. CMS caused an increase in the methylation of the third Gpx4 promoter in peripheral blood mononuclear cells and Gpx1 promoter in the cerebral cortex. Additionally, stressed rats treated with agomelatine displayed a significantly lower Gpx4 level in the hypothalamus. The results confirm the hypothesis that the CMS procedure and agomelatine administration change the expression level and methylation status of the promoter region of genes involved in oxidative and nitrosative stress.

scholarly journals Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
M. Neri ◽  
I. Riezzo ◽  
C. Pomara ◽  
S. Schiavone ◽  
E. Turillazzi
Keyword(s):  
Oxidative Stress ◽  
Current Literature ◽  
Cardiac Dysfunction ◽  
Nitrosative Stress ◽  
Myocardial Dysfunction ◽  
Critical Role ◽  
Therapeutic Effects ◽  
Oxidative And Nitrosative Stress ◽  
Antioxidant Agents

Background. Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients.Aim. In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis.Conclusions. Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents.

Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Injury through Modulation of the Nrf2/HO−1 and NF-kB Pathways

2021 ◽  
Vol 28 ◽  
Author(s):  
Roberta Fusco ◽  
Rosalba Siracusa ◽  
Enrico Gugliandolo ◽  
Alessio Filippo Peritore ◽  
Ramona D’Amico ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adhesion Molecules ◽  
Vascular Injury ◽  
Nitrosative Stress ◽  
Neointimal Hyperplasia ◽  
Vascular Damage ◽  
Oxidative And Nitrosative Stress ◽  
Monocyte Chemoattractant Protein 1 ◽  
Vessel Morphology ◽  
And Oxidative Stress

Background: Vascular remodeling processes induced by acute and chronic injuries are characterized by inflammation and oxidative stress. In arteriosclerosis, atherosclerosis and restenosis, the progression of neointimal hyperplasia is a key event of vascular damage. Objective: Our study was aimed to investigate the inflammation and oxidative stress development during vascular impairment and the potential efficacy of treatment of new micro composite N-palmitoylethanolamine /Rutin at a ratio of 1:1 (PEA/RUT). The anti-inflammatory effects of Palmitoylethanolamide (PEA) are well known. Rutin has important pharmacological actions, including antioxidant and vasoprotective. Methods: As model of vascular injury we used the complete ligature of the left carotid artery for fourteen days and administered PEA/RUT at the dose of 10 mg/Kg. Results: This study demonstrated that after fourteen days carotid ligation there is a substantial structural change in the vessel morphology, with inflammatory cells infiltration and reactive oxygen species production. PEA/RUT administration reduced change in vascular morphology, cytokines like monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules expression like intercellular adhesion molecules-1 (ICAM-1), proinflammatory cytokines production (IL-1, IL-6 and TNF-), oxidative and nitrosative stress (nitrotyrosine and PARP expression and NRF2 pathway). Conclusions: Our data clearly demonstrate the beneficial effect of PEA/RUT administration in reducing inflammation, oxidative stress and vascular damage.

ROLE OF PREGNAN-X-RECEPTOR IN CELL RESISTANCE TO NITROSATIVE AND OXIDATIVE STRESS

2021 ◽  
Author(s):  
Yulia Abalenikhina ◽  
◽  
Elena A. Sudakova ◽  
Pelageya Erokhina ◽  
Aleksey Shchulkin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Viability ◽  
Nitrosative Stress ◽  
Pregnane X Receptor ◽  
Cell Resistance ◽  
Oxidative And Nitrosative Stress ◽  
High Concentrations ◽  
And Oxidative Stress

The article discusses the new role of pregnane X receptor (PXR) under conditions of oxidative and nitrosative stress. The results showed that the effect of hydrogen peroxide and S-nitrosoglu-tathione in high concentrations on Caco-2 cells leads to a decrease in cell viability, which is accompanied by an increase in the amount of PXR. These changes are offset by the addition of ketoconazole (inhibitor of PXR) to the medium.

Sign in / Sign up

Export Citation Format

Share Document