Peroxynitrite, lung disease

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system...

BACKGROUND: The cellular endoplasmic reticulum (ER) is responsible for various functions, including protein synthesis, folding, distribution, and calcium ion storage. Studies have linked ER stress with acute lung injury (ALI), which can result in oxidative stress and even cell death. Peroxynitrite (ONOO- ) is a well-known reactive oxygen species (ROS) that contributes to various physiological and pathological processes in oxidative stress diseases. To understand the role of ER ONOO- in ALI, it is crucial to accurately measure its level in the ER...

A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or "good stress" and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2-related factor 2 (Nrf2) and other processes...

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. In addition to chronic bronchitis and emphysema, patients often develop at least mild pulmonary hypertension (PH). We previously demonstrated that inhibition of inducible nitric oxide synthase (iNOS) prevents and reverses emphysema and PH in mice. Interestingly, strong iNOS upregulation was found in alveolar epithelial type II cells (AECII) in emphysematous murine lungs, and peroxynitrite, which can be formed from iNOS-derived NO, was shown to induce AECII apoptosis in vitro...

Pulmonary fibrosis is common in the development of inflammatory lung diseases with no effective clinical drug treatment currently. As an essential redox enzyme, thioredoxin (Trx) has been reported to be involved in pulmonary fibrosis, but the mechanism is to be revealed. Therefore, in bleomycin-indued pulmonary fibrosis model in C57 mice, Trx activity and nitrated Trx were examined.,p38-MAPK apoptosis pathway was determined in lung tissues. Additionally, before BLM administration, C57/BL6 mice were treated with aminoguanidine (AG, a peroxynitrite scavenger), recombinant human Trx-1 (rhTrx-1), or SIN-1 (a peroxynitrite donor) nitrated Trx-1 (N-Trx-1)...

Idiopathic pulmonary fibrosis (IPF) has been characterized as a chronic inflammatory disease that leads to irreversible damage to pulmonary function. However, there is no specific IPF biomarker that can be used to distinguish IPF and not pneumonia. Endoplasmic reticulum (ER) stress is prominent in IPF. To search for a specific biomarker of IPF, we developed two ER-targeting two-photon (TP) fluorescent probes, TPER -ONOO and TPER -Cys, for peroxynitrite (ONOO- ) and cysteine (Cys) imaging, respectively. A significant increase in Cys levels in the lungs was discovered only in mice with IPF, which implied that Cys might be an IPF biomarker candidate...

PURPOSE: To identify plasma alterations in lipid species in patients with chronic obstructive pulmonary disease (COPD), as well as, relationships with smoking status, oxidative and inflammatory markers. METHODS: Plasma was obtained from 100 patients with COPD and 120 healthy controls. Pulmonary function was assessed by plethysmography. Serum levels of IL-6 and TNF-α were determined by ELISA. Oxidative stress parameters were measured using standard methods. Lipids were extracted then analyzed by Matrix-Assisted Laser Desorption and Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-TOF-MS)...

Current coronavirus disease (COVID-19) is regarded as a primary respiratory and vascular disease leading to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and endothelial dysfunction (ED) in severe cases. The causative virus of COVID-19 is SARS-CoV-2, which binds angiotensin-converting enzyme 2 (ACE2) for its entry. It has been shown that ED is linked to various COVID-19 complications since endothelial cells are regarded as the chief barrier against SARS-CoV- 2 invasion. SARS-CoV-2-indued ED leads to endotheliitis and thrombosis due to endothelial nitric oxide (NO) inhibition with subsequent vasoconstriction and tissue hypoxia...

Airway epithelium forms a physical barrier that protects the lung from the entrance of inhaled allergens, irritants, or microorganisms. This epithelial structure is maintained by tight junctions, adherens junctions and desmosomes that prevent the diffusion of soluble mediators or proteins between apical and basolateral cell surfaces. This apical junctional complex also participates in several signaling pathways involved in gene expression, cell proliferation and cell differentiation. In addition, the airway epithelium can produce chemokines and cytokines that trigger the activation of the immune response...

Asthma is a chronic inflammatory disease of the airways related to epithelial damage, bronchial hyperresponsiveness to contractile agents, tissue remodeling, and luminal narrowing. Currently, there are many data about the pathophysiology of asthma; however, a new aspect has emerged related to the influence of reactive oxygen and nitrogen species (ROS and RNS) on the origin of this disease. Several studies have shown that an imbalance between the production of ROS and RNS and the antioxidant enzymatic and nonenzymatic systems plays an important role in the pathogenesis of this disease...

BACKGROUND: Cathepsin D (CTSD) is an aspartyl proteinase that plays an important role in protein degradation, antigen processing and apoptosis. It has been associated with several pathologies such as cancer, Alzheimer's disease and inflammatory disorders. Its function in lung diseases remains, however, controversial. In the current study, we determined CTSD activity in serum of patients with chronic obstructive pulmonary disease (COPD) and evaluated the correlations between this proteinase and inflammatory and oxidative parameters...

BACKGROUND: Exposure to traffic-generated emissions is associated with the development and exacerbation of inflammatory lung disorders such as chronic obstructive pulmonary disorder (COPD) and idiopathic pulmonary fibrosis (IPF). Although many lung diseases show an expansion of Proteobacteria, the role of traffic-generated particulate matter pollutants on the lung microbiota has not been well-characterized. Thus, we investigated the hypothesis that exposure to diesel exhaust particles (DEP) can alter commensal lung microbiota, thereby promoting alterations in the lung's immune and inflammatory responses...

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and death worldwide. Peroxynitrite, formed from nitric oxide, which is derived from inducible nitric oxide synthase, and superoxide, has been implicated in the development of emphysema, but the source of the superoxide was hitherto not characterized. Here, we identify the non-phagocytic NADPH oxidase organizer 1 (NOXO1) as the superoxide source and an essential driver of smoke-induced emphysema and pulmonary hypertension development in mice...

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 (O2 -), Hydrogen Peroxide (H2 O2 ) 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...

Exposure to hog barn organic dust contributes to occupational lung diseases, which are mediated by inflammatory and oxidative stress pathways. Isoprostanes-a family of eicosanoids produced by oxidation of phospholipids by oxygen radicals-are biomarkers of pulmonary oxidative stress. Importantly, 8-isoprostane has been implicated as a key biomarker and mediator of oxidative stress because it is a potent pulmonary vasoconstrictor. Antioxidants found in fruits and vegetables hold promise for preventing or reducing effects of oxidative stress-related diseases including chronic bronchitis and chronic obstructive pulmonary disease (COPD)...

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with short survival time. However, owing to the unknown etiology and the lack of sensitive and noninvasive methods, the diagnosis of IPF in the early stage is still full of challenges. Since the levels of oxidative stress in mitochondria are relevant to pulmonary fibrosis, we herein present a simultaneous near-infrared (NIR)-Ia window and ratiometic fluorescent probe, rTPONOO-1, with two-photon and mitochondria-targeting abilities to explore the potential biological roles of peroxynitrite (ONOO- ) in different states of lung slices from healthy to lung inflammation and pulmonary fibrosis, and there is a good linear relationship between ratiometric fluorescence changes and the rate of pulmonary fibrosis from hematoxylin and eosin (H&E) and Masson staining...

INTRODUCTION: Cough exceeding 3-8 weeks was defined as chronic cough in various guides. Asthma is the most common cause of chronic-specific cough. Causes other than asthma include prolonged bacterial bronchitis and upper airway cough syndrome (UACS). Nitric oxide (NO) causes vascular smooth muscle relaxation, bronchodilation, and oxidant effects via its metabolite, peroxynitrite. An increase in NO results in inflammation, vasodilatation, and bronchial edema. MATERIALS AND METHODS: The study group included 90 patients aged 6-17 years selected from individuals presenting to the Pediatric Immunology and Allergic Diseases Clinic with cough persisting for 4 weeks and 30 other patients representing to the control group...

Peroxynitrite is a powerful oxidant, formed from the reaction of nitric oxide and superoxide. It is known to interact and modify different biological molecules such as DNA, lipids and proteins leading to alterations in their structure and functions. These events elicit various cellular responses, including cell signaling, causing oxidative damage and committing cells to apoptosis or necrosis. This review discusses nitrosative stress-induced modification in the DNA molecule that results in the formation of 8-nitroguanine and 8-oxoguanine, and its role in disease conditions...

Identification of factors contributing to the development of chronic obstructive pulmonary disease (COPD) is crucial for developing new treatments. An increase in the levels of protein-disulfide isomerase (PDI), a multifaceted endoplasmic reticulum resident chaperone, has been demonstrated in human smokers, presumably as a protective adaptation to cigarette smoke (CS) exposure. We found a similar increase in the levels of PDI in the murine model of COPD. We also found abnormally high levels (4-6 times) of oxidized and sulfenilated forms of PDI in the lungs of murine smokers compared with non-smokers...

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. No therapy stopping progress of the disease is available. OBJECTIVES: To investigate the role of the soluble guanylate cyclase (sGC)-cGMP axis in development of lung emphysema and pulmonary hypertension (PH) and to test whether the sGC-cGMP axis is a treatment target for these conditions. METHODS: Investigations were performed in human lung tissue from patients with COPD, healthy donors, mice, and guinea pigs...