III. A molecular prelude to intestinal inflammation

1999 ◽  
Vol 276 (4) ◽  
pp. G795-G799 ◽  
Author(s):  
Mark J. S. Miller ◽  
Manuel Sandoval
Keyword(s):  
Nitric Oxide ◽  
Nitrogen Oxides ◽  
Chronic Inflammation ◽  
Intestinal Inflammation ◽  
Tissue Injury ◽  
Direct Interaction ◽  
Oxides Of Nitrogen ◽  
Anti Inflammatory ◽  
Oxide Synthase

Nitric oxide (NO) synthesis is markedly augmented in states of inflammation, largely due to the expression of inducible nitric oxide synthase (iNOS). Although NO has anti-inflammatory consequences under basal conditions, it remains enigmatic as to why NO displays proinflammatory characteristics in chronic inflammation. Either the anti-inflammatory actions are weak and of little consequence or, alternatively, other factors influence the role of NO in chronic inflammation. We propose that the answer to this enigma lies in the conversion of NO to other higher oxides of nitrogen (NO2, nitrogen dioxide; N2O3, dinitrogen trioxide; and ONOO−, peroxynitrite). Emerging therapeutic strategies may be independent of NO synthesis; e.g., antioxidants have no direct interaction with NO but attenuate the levels and activity of higher nitrogen oxides. Thus, whereas iNOS may be a marker for the proinflammatory actions of NO, the species that mediate tissue injury/dysfunction in inflammation are likely to be nitrogen oxides other than NO.

V. Therapeutic potential of nitric oxide donors and inhibitors

1999 ◽  
Vol 276 (6) ◽  
pp. G1313-G1316 ◽  
Author(s):  
Marcelo N. Muscará ◽  
John L. Wallace
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Mucosal Injury ◽  
Therapeutic Agents ◽  
Gastrointestinal Physiology ◽  
Inflammatory Drugs ◽  
Nitric Oxide Releasing ◽  
Oxide Synthase

Nitric oxide is a crucial mediator of gastrointestinal mucosal defense, but, paradoxically, it also contributes to mucosal injury in several situations. Inhibitors of nitric oxide synthesis and compounds that release nitric oxide have been useful pharmacological tools for evaluating the role of nitric oxide in gastrointestinal physiology and pathophysiology. Newer inhibitors with selectivity for one of the isoforms of nitric oxide synthase are even more powerful tools and may have utility as therapeutic agents. Also, agents that can scavenge nitric oxide or peroxynitrite are promising as drugs to prevent nitric oxide-associated tissue injury. Compounds that release nitric oxide in small amounts over a prolonged period of time may also be very useful for prevention of gastrointestinal injury associated with shock and with the use of drugs that have ulcerogenic effects. Indeed, the coupling of a nitric oxide-releasing moiety to nonsteroidal anti-inflammatory drugs has proven to be a valid means of substantially reducing the gastrointestinal toxicity of these drugs without decreasing their efficacy.

scholarly journals I. Physiological chemistry of nitric oxide and its metabolites: implications in inflammation

1999 ◽  
Vol 276 (2) ◽  
pp. G315-G321 ◽  
Author(s):  
Matthew B. Grisham ◽  
David Jourd’Heuil ◽  
David A. Wink
Keyword(s):  
Nitric Oxide ◽  
Indirect Effects ◽  
Tissue Injury ◽  
No Production ◽  
Physiological Chemistry ◽  
Reactive Nitrogen Oxide Species ◽  
Anti Inflammatory ◽  
The Many ◽  
Active Inflammation

The role of nitric oxide (NO) in inflammation represents one of the most studied yet controversial subjects in physiology. A number of reports have demonstrated that NO possesses potent anti-inflammatory properties, whereas an equally impressive number of studies suggest that NO may promote inflammation-induced cell and tissue dysfunction. The reasons for these apparent paradoxical observations are not entirely clear; however, we propose that understanding the physiological chemistry of NO and its metabolites will provide a blueprint by which one may distinguish the regulatory/anti-inflammatory properties of NO from its deleterious/proinflammatory effects. The physiological chemistry of NO is complex and encompasses numerous potential reactions. In an attempt to simplify the understanding of this chemistry, the physiological aspects of NO chemistry may be categorized into direct and indirect effects. This type of classification allows for consideration of timing, location, and rate of production of NO and the relevant targets likely to be affected. Direct effects are those reactions in which NO interacts directly with a biological molecule or target and are thought to occur under normal physiological conditions when the rates of NO production are low. Generally, these types of reactions may serve regulatory and/or anti-inflammatory functions. Indirect effects, on the other hand, are those reactions mediated by NO-derived intermediates such as reactive nitrogen oxide species derived from the reaction of NO with oxygen or superoxide and are produced when fluxes of NO are enhanced. We postulate that these types of reactions may predominate during times of active inflammation. Consideration of the physiological chemistry of NO and its metabolites will hopefully allow one to identify which of the many NO-dependent reactions are important in modulating the inflammatory response and may help in the design of new therapeutic strategies for the treatment of inflammatory tissue injury.

scholarly journals Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Talero Elena ◽  
Di Paola Rosanna ◽  
Mazzon Emanuela ◽  
Emanuela Esposito ◽  
Motilva Virginia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Tissue Injury ◽  
Inflammatory Factors ◽  
Amino Acid Peptide ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors.

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

Vasculoprotective Role of Inducible Nitric Oxide Synthase at Inflammatory Coronary Lesions Induced by Chronic Treatment With Interleukin-1β in Pigs in Vivo

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3104-3111 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa ◽  
Toshiyuki Kozai ◽  
Toshiaki Kadokami ◽  
Kouichi Kuwata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Chronic Treatment ◽  
Interleukin 1Β ◽  
Coronary Lesions ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

Neuronal nitric oxide synthase and systemic vasodilation in rats with cirrhosis

2000 ◽  
Vol 279 (6) ◽  
pp. F1110-F1115 ◽  
Author(s):  
Lieming Xu ◽  
Ethan P. Carter ◽  
Mamiko Ohara ◽  
Pierre-Yves Martin ◽  
Boris Rogachev ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Cirrhosis ◽  
Nitric Oxide Synthase ◽  
Control Treatment ◽  
Sodium Balance ◽  
Hyperdynamic Circulation ◽  
Molecular Approaches ◽  
Advanced Liver Cirrhosis ◽  
Oxide Synthase

Cirrhosis is typically associated with a hyperdynamic circulation consisting of low blood pressure, low systemic vascular resistance (SVR), and high cardiac output. We have recently reported that nonspecific inhibition of nitric oxide synthase (NOS) with nitro-l-arginine methyl ester reverses the hyperdynamic circulation in rats with advanced liver cirrhosis induced by carbon tetrachloride (CCl4). Although an important role for endothelial NOS (eNOS) is documented in cirrhosis, the role of neuronal NOS (nNOS) has not been investigated. The present study was carried out to specifically investigate the role of nNOS during liver cirrhosis. Specifically, physiological, biochemical, and molecular approaches were employed to evaluate the contribution of nNOS to the cirrhosis-related hyperdynamic circulation in CCl4-induced cirrhotic rats with ascites. Cirrhotic animals had a significant increase in water and sodium retention. In the aorta from cirrhotic animals, both nNOS protein expression and cGMP concentration were significantly elevated compared with control. Treatment of cirrhotic rats for 7 days with the specific nNOS inhibitor 7-nitroindazole (7-NI) normalized the low SVR and mean arterial pressure, elevated cardiac index, and reversed the positive sodium balance. Increased plasma arginine vasopressin concentrations in the cirrhotic animals were also repressed with 7-NI in association with diminished water retention. The circulatory changes were associated with a reduction in aortic nNOS expression and cGMP. However, 7-NI treatment did not restore renal function in cirrhotic rats (creatinine clearance: 0.76 ± 0.03 ml · min−1· 100 g body wt−1in cirrhotic rats vs. 0.79 ± 0.05 ml · min−1· 100 g body wt−1in cirrhotic rats+7-NI; P NS.). Taken together, these results indicate that nNOS-derived NO contributes to the development of the hyperdynamic circulation and fluid retention in cirrhosis.

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