https://staff.blog.ui.ac.id/hsuryadi/files/2012/02/ROS_RNS.pdf

Free radicals and antioxidants in normal physiological functions and human disease

Free radicals, metals and antioxidants in oxidative stress-induced cancer

For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

/pdf/the-nox-family-of-ros-generating-nadph-oxidases-physiology-zjc88zvh59.pdf

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

/pdf/nitric-oxide-and-peroxynitrite-in-health-and-disease-3uuuqgfdcz.pdf

Nitric Oxide and Peroxynitrite in Health and Disease

WITH increasing frequency, the human neutrophil is being implicated as a mediator of tissue-destructive events in inflammatory diseases ranging from rheumatoid arthritis and myocardial reperfusion injury to respiratory distress syndromes, blistering skin disorders, and ulcerative colitis.1 , 2 In each of these diseases, as well as a variety of other acute inflammatory disorders, important components of these pathologic processes are being linked to the neutrophil's ability to release a complex assortment of agents that can destroy normal cells and dissolve connective tissues. Although these toxins normally defend the host against invading microbes, the neutrophil has little intrinsic ability to differentiate between foreign . . .

Tissue Destruction by Neutrophils

Previous studies have revealed that the expression of several endothelial cell adhesion molecules [e.g., intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and ...

https://www.physiology.org/doi/pdf/10.1152/ajpgi.2001.281.5.G1309

MAdCAM mediates lymphocyte-endothelial cell adhesion in a murine model of chronic colitis

https://www.gastrojournal.org/article/S0016-5085(88)80073-8/pdf

Inflammation-induced intestinal hyperemia in the rat: role of neutrophils.

Increased disease activity in eNOS-deficient mice in experimental colitis

Exhaled nitric oxide (NO) is increased in some inflammatory airway disorders but not in others such as cystic fibrosis and acute respiratory distress syndrome. NO can combine with superoxide ( O 2 ...

Superoxide released from neutrophils causes a reduction in nitric oxide gas

The objective of this study was to define the relationship between peroxyl radical-mediated cytotoxicity and lipid, protein and sulfhydryl oxidation using human erythrocytes as the target mammalian cell. We found that incubation of human erythrocytes with the peroxyl radical generator 2,2' azobis (2-amidinopropane) hydrochloride (AAPH) resulted in a time and dose-dependent increase in hemolysis such that at 50 mM AAPH maximum hemolysis was achieved at 120 min. Hemolysis was inhibited by hypoxia and by the addition of certain water soluble free radical scavengers such as 5-aminosalicylic acid (5-ASA), 4-ASA, N-acetyl-5-ASA and dimethyl thiourea. Peroxyl radical-mediated hemolysis did not appear to involve significant peroxidation of erythrocyte lipids nor did they enhance protein oxidation at times preceding hemolysis. Peroxyl radicals did however, significantly reduce by approximately 80% the intracellular levels of GSH and inhibit by approximately 90% erythrocyte Ca(2+)-Mg2+ ATPase activity at times preceding the hemolytic event. Our data as well as others suggest that extracellular oxidants promote the oxidation of intracellular compounds by interacting with certain redox active membrane components. Depletion of intracellular GSH stores using diamide did not result in hemolysis suggesting that oxidation of GSH alone does not promote hemolysis. Taken together, our data suggest that neither GSH oxidation, lipid peroxidation nor protein oxidation alone can account for peroxyl radical-mediated hemolysis. It remains to be determined whether free radical-mediated inactivation of Ca(2+)-Mg2+ ATPase is an important mechanism in this process.

Matthew B. Grisham

Papers

MAdCAM mediates lymphocyte-endothelial cell adhesion in a murine model of chronic colitis

Inflammation-induced intestinal hyperemia in the rat: role of neutrophils.

Increased disease activity in eNOS-deficient mice in experimental colitis

Superoxide released from neutrophils causes a reduction in nitric oxide gas

Peroxyl radical-mediated hemolysis: role of lipid, protein and sulfhydryl oxidation.