Oxidative Stress in COPD

https://link.springer.com/content/pdf/10.1097%2FWOX.0b013e318232389e.pdf

Oxidative Stress in Asthma

Chronic asthma is an inflammatory airways disease characterized by pathological changes in the airway smooth muscle (ASM) bundle that contribute to airway obstruction and hyperresponsiveness. Remodeling of the ASM is associated with an increased smooth muscle mass, involving components of cellular hypertrophy and hyperplasia, and changes in the phenotype of the muscle that facilitate proliferative, synthetic and contractile functions. These changes are considered major contributing factors to the pathophysiology of asthma, because of their role in exaggerated airway narrowing. The mechanisms that regulate changes in ASM mass and phenotype are incompletely understood, but likely involve the regulatory role of mediators and growth factors secreted from inflammatory cells on ASM cell proliferation and phenotype. An alternative hypothesis is that cellular and structural components that together constitute the airway wall, such as the airway epithelium, airway nerves, and the extracellular matrix, interact with the ASM bundle to facilitate changes in smooth muscle phenotype and function that drive remodeling under inflammatory conditions. This review discusses the mechanisms by which structural components of the airway wall communicate with the ASM bundle to regulate remodeling and discusses these mechanisms in the context of the pathophysiology of asthma.

https://www.atsjournals.org/doi/pdf/10.1513/pats.200907-056DP

Airway Structural Components Drive Airway Smooth Muscle Remodeling in Asthma

Recent studies have indicated that arginase, which converts l-arginine into l-ornithine and urea, may play an important role in the pathogenesis of various pulmonary disorders. In asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis, increased arginase activity in the airways may contribute to obstruction and hyperresponsiveness of the airways by inducing a reduction in the production of bronchodilatory nitric oxide (NO) that results from its competition with constitutive (cNOS) and inducible (iNOS) NO synthases for their common substrate. In addition, reduced l-arginine availability to iNOS induced by arginase may result in the synthesis of both NO and the superoxide anion by this enzyme, thereby enhancing the production of peroxynitrite, which has procontractile and pro-inflammatory actions. Increased synthesis of l-ornithine by arginase may also contribute to airway remodelling in these diseases. l-Ornithine is a precursor of polyamines and l-proline, and these metabolic products may promote cell proliferation and collagen production, respectively. Increased arginase activity may also be involved in other fibrotic disorders of the lung, including idiopathic pulmonary fibrosis. Finally, through its action of inducing reduced levels of vasodilating NO, increased arginase activity has been associated with primary and secondary forms of pulmonary hypertension. Drugs targeting the arginase pathway could have therapeutic potential in these diseases.

/pdf/arginase-and-pulmonary-diseases-156al6nr08.pdf

Arginase and pulmonary diseases.

Allergic asthma is a chronic inflammatory airways' disease, characterized by allergen-induced early and late bronchial obstructive reactions, airway hyperresponsiveness (AHR), airway inflammation and airway remodelling. Recent ex vivo and in vivo studies in animal models and asthmatic patients have indicated that arginase may play a central role in all these features. Thus, increased arginase activity in the airways induces reduced bioavailability of L-arginine to constitutive (cNOS) and inducible (iNOS) nitric oxide synthases, causing a deficiency of bronchodilating and anti-inflammatory NO, as well as increased formation of peroxynitrite, which may be involved in allergen-induced airways obstruction, AHR and inflammation. In addition, both via reduced NO production and enhanced synthesis of L-ornithine, increased arginase activity may be involved in airway remodelling by promoting cell proliferation and collagen deposition in the airway wall. Therefore, arginase inhibitors may have therapeutic potential in the treatment of acute and chronic asthma. This review focuses on the pathophysiological role of arginase in allergic asthma and the emerging effectiveness of arginase inhibitors in the treatment of this disease.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.2009.00374.x

Arginase: a key enzyme in the pathophysiology of allergic asthma opening novel therapeutic perspectives

1. In the present study, the roles of nitric oxide (NO) and superoxide anions (O2(-)) in allergen-induced airway hyperreactivity (AHR) after the late asthmatic reaction (LAR) were investigated ex vivo, by examining the effects of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) and superoxide dismutase (SOD) on the responsiveness to methacholine of isolated perfused guinea-pig tracheae from unchallenged (control) animals and from animals 24 h after ovalbumin challenge. 2. At 24 h after allergen challenge, the animals developed AHR in vivo, as indicated by a mean 2.63 +/- 0.54 fold (P < 0.05) increase in sensitivity to histamine inhalation. 3. Compared to unchallenged controls, tracheal preparations from the ovalbumin-challenged guinea-pigs displayed a significant 1.8 fold (P < 0.01) increase in the maximal response (E(max)) to methacholine, both after intraluminal (IL) and extraluminal (EL) administration of the agonist. No changes were observed in the sensitivity (pEC(50)) to the agonist. Consequently, the DeltapEC(50) (EL-IL), as a measure of epithelial integrity, was unchanged. 4. In the presence of L-NAME (100 microM, IL), tracheae from control guinea-pigs showed a 1.6 fold (P < 0.05) increase in the E(max) of IL methacholine. By contrast, the E(max) of IL methacholine was significantly decreased in the presence of 100 u ml(-1) EL SOD (54% of control, P < 0.01). 5. Remarkably, the increased responsiveness to IL methacholine at 24 h after allergen challenge was reversed by L-NAME to control (P < 0.01), and a similar effect was observed with SOD (P < 0.01). 6. The results indicate that both NO and O2(-) are involved in the tracheal hyperreactivity to methacholine after the LAR, possibly by promoting airway smooth muscle contraction through the formation of peroxynitrite.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0704191

Role of nitric oxide and superoxide in allergen-induced airway hyperreactivity after the late asthmatic reaction in guinea-pigs

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Miranda Koopal

Author Tools

Chat about Author

Papers

Role of nitric oxide and superoxide in allergen-induced airway hyperreactivity after the late asthmatic reaction in guinea-pigs