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

Regional differences and magnitude of endothelial cell adhesion molecule expression in scid mice reconstituted with CD45RBHIGH T-lymphocytes

Reactive metabolites of oxygen and nitrogen, NF-κB and chronic inflammation

Role of nitric oxide in regulating cytokine expression and tissue injury in postischemic liver injury

The inflammatory bowel diseases (IBD; Crohn’s disease, ulcerative colitis) are chronic, idiopathic inflammatory disorders of the intestine and/or colon characterized by rectal bleeding, severe diarrhea, abdominal pain, fever and weight loss Histologic examination of biopsies obtained from patients with active episodes of IBD reveal the infiltration of large numbers of leukocytes such as polymorphonuclear leukocytes (PMNs), monocytes, and lymphocytes into the intestinal interstitium Extensive mucosal and/or transmural injury and dysfunction including edema, loss of goblet cells, decreased mucous production, crypt cell hyperplasia, erosions and ulcerations, accompany this inflammatory infiltrate Despite several years of intense investigation, the etiology and specific pathogenetic mechanisms responsible for IBD remain poorly defined Recent experimental and clinical studies suggest that the initiation and pathogenesis of these diseases are multi-factorial involving interactions among genetic, environmental and immune factors [1] Regardless of exactly how these interactions ultimately promote chronic gut inflammation, it is becoming increasingly apparent that the immune system plays a crucial role in disease pathogenesis Because the inflammation is localized primarily to the intestinal tract in IBD, investigators have focused on the intestinal lumen as the site for the antigenic trigger Indeed, the chronic relapsing nature of IBD coupled to the fact that a large percentage of patients with Crohn’s disease will experience recurrence of the disease following surgical resection of the bowel, suggests that the antigen or antigens that initiate and perpetuate this disease are part of the normal gut flora Different etio-logic theories have been proposed to account for this apparent mucosal immune system activation, however, data obtained from numerous experimental studies suggest that chronic gut inflammation may result from a dysregulated immune response to components of the normal gut flora [2] For example, several groups of investigators have shown that targeted deletion of certain genes known to be important in regulating the inflammatory response or immune manipulation in mice induces chronic colitis in these animals [3] Furthermore, the colonic inflammation observed in virtually all of these animal models is dependent upon the presence of normal gut flora Animals raised under germ-free conditions either fail to develop disease or develop much milder forms of colitis [3] These studies have lead investigators to suggest that bacterial/immune interactions in individuals with defects in their immune system may represent an important pathophysiological mechanism for the development of IBD in humans

Matthew B. Grisham

Papers

Regional differences and magnitude of endothelial cell adhesion molecule expression in scid mice reconstituted with CD45RBHIGH T-lymphocytes

Reactive metabolites of oxygen and nitrogen, NF-κB and chronic inflammation

Role of nitric oxide in regulating cytokine expression and tissue injury in postischemic liver injury

Role of nitric oxide in chronic gut inflammation

Role of different nitric oxide synthese (NOS) isoforms in the regulation of endothelial cell adhesion molecule (ECAM) expression in vivo