scholarly journals Partial deletion of argininosuccinate synthase protects from pyrazole plus lipopolysaccharide-induced liver injury by decreasing nitrosative stress

2012 ◽  
Vol 302 (3) ◽  
pp. G287-G295 ◽  
Author(s):  
Yongke Lu ◽  
Tung Ming Leung ◽  
Stephen C. Ward ◽  
Natalia Nieto
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
Nitrosative Stress ◽  
Neutrophil Infiltration ◽  
Positive Staining ◽  
Neutrophil Accumulation ◽  
Argininosuccinate Synthase ◽  
Relevant Role ◽  
Oxide Synthase

Argininosuccinate synthase (ASS) is the rate-limiting enzyme in the urea cycle. Along with nitric oxide synthase (NOS)-2, ASS endows cells with the l-citrulline/nitric oxide (NO·) salvage pathway to continually supply l-arginine from l-citrulline for sustained NO· generation. Because of the relevant role of NOS in liver injury, we hypothesized that downregulation of ASS could decrease the availability of intracellular substrate for NO· synthesis by NOS-2 and, hence, decrease liver damage. Previous work demonstrated that pyrazole plus LPS caused significant liver injury involving NO· generation and formation of 3-nitrotyrosine protein adducts; thus, wild-type (WT) and Ass+/−mice ( Ass−/−mice are lethal) were treated with pyrazole plus LPS, and markers of nitrosative stress, as well as liver injury, were analyzed. Partial ablation of Ass protected from pyrazole plus LPS-induced liver injury by decreasing nitrosative stress and hepatic and circulating TNFα. Moreover, apoptosis was prevented, since pyrazole plus LPS-treated Ass+/−mice showed decreased phosphorylation of JNK; increased MAPK phosphatase-1, which is known to deactivate JNK signaling; and lower cleaved caspase-3 than treated WT mice, and this was accompanied by less TdT-mediated dUTP nick end labeling-positive staining. Lastly, hepatic neutrophil accumulation was almost absent in pyrazole plus LPS-treated Ass+/−compared with WT mice. Partial Ass ablation prevents pyrazole plus LPS-mediated liver injury by reducing nitrosative stress, TNFα, apoptosis, and neutrophil infiltration.

scholarly journals Protection against acetaminophen-induced liver injury and lethality by interleukin 10: Role of inducible nitric oxide synthase

Hepatology ◽  
2002 ◽  
Vol 35 (2) ◽  
pp. 289-298 ◽  
Author(s):  
Mohammed Bourdi ◽  
Yasuhiro Masubuchi ◽  
Timothy P. Reilly ◽  
Hamid R. Amouzadeh ◽  
Jackie L. Martin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Liver Injury ◽  
Inducible Nitric Oxide Synthase ◽  
Interleukin 10 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Effect of Aminoguanidine in Ligature-induced Periodontitis in Rats

2004 ◽  
Vol 83 (4) ◽  
pp. 343-348 ◽  
Author(s):  
R. Di Paola ◽  
S. Marzocco ◽  
E. Mazzon ◽  
F. Dattola ◽  
F. Rotondo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Alveolar Bone ◽  
Bone Destruction ◽  
Neutrophil Infiltration ◽  
Positive Staining ◽  
Nitric Oxide Synthase Inhibitor ◽  
Inflammatory Parameters ◽  
Synthase Inhibitor ◽  
Oxide Synthase

The role of nitric oxide and reactive oxygen species is well-demonstrated in inflammation. In this study, we evaluated the effect of aminoguanidine, a nitric oxide synthase inhibitor, in a rat model of periodontitis. We induced periodontitis in rats by placing a piece of 2/0 braided silk around the lower left 1st molar. At day 8, the gingivomucosal tissue encircling the mandibular 1st molar was removed for biochemical and histological analysis. Ligation significantly increased inducible nitric oxide synthase activity and expression, and damaged tissue revealed increased neutrophil infiltration, lipid peroxidation, and positive staining for nitrotyrosine formation and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Aminoguanidine (100 mg/kg i.p., daily for 8 days) treatment significantly reduced all these inflammatory parameters, indicating that it protects against the tissue damage associated with periodontitis by reducing nitric oxide production and oxidative stress.

scholarly journals Experimental Model of Zymosan-Induced Arthritis in the Rat Temporomandibular Joint: Role of Nitric Oxide and Neutrophils

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Hellíada Vasconcelos Chaves ◽  
Ronaldo de Albuquerque Ribeiro ◽  
André Mattos Brito de Souza ◽  
Antonio Alfredo Rodrigues e Silva ◽  
Antoniella Souza Gomes ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Temporomandibular Joint ◽  
Myeloperoxidase Activity ◽  
Plasma Extravasation ◽  
Neutrophil Accumulation ◽  
Histological Changes ◽  
Leucocyte Migration ◽  
Nos Inhibitors ◽  
Oxide Synthase

Aims. To establish a new model of zymosan-induced temporomandibular joint (TMJ) arthritis in the rat and to investigate the role of nitric oxide.Methods. Inflammation was induced by an intra-articular injection of zymosan into the left TMJ. Mechanical hypernociception, cell influx, vascular permeability, myeloperoxidase activity, nitrite levels, and histological changes were measured in TMJ lavages or tissues at selected time points. These parameters were also evaluated after treatment with the nitric oxide synthase (NOS) inhibitors L-NAME or 1400 W.Results. Zymosan-induced TMJ arthritis caused a time-dependent leucocyte migration, plasma extravasation, mechanical hypernociception, and neutrophil accumulation between 4 and 24 h. TMJ immunohistochemical analyses showed increased inducible NOS expression. Treatment with L-NAME or 1400 W inhibited these parameters.Conclusion. Zymosan-induced TMJ arthritis is a reproducible model that may be used to assess both the mechanisms underlying TMJ inflammation and the potential tools for therapies. Nitric oxide may participate in the inflammatory temporomandibular dysfunction mechanisms.

scholarly journals Paradoxical Role of Matrix Metalloproteinases in Liver Injury and Regeneration after Sterile Acute Hepatic Failure

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 247 ◽  
Author(s):  
Débora Alvarenga ◽  
Matheus Mattos ◽  
Mateus Lopes ◽  
Sarah Marchesi ◽  
Alan Araújo ◽  
...  
Keyword(s):  
Liver Injury ◽  
Matrix Metalloproteinases ◽  
Hepatic Failure ◽  
Acute Hepatic Failure ◽  
Neutrophil Infiltration ◽  
Hepatic Necrosis ◽  
Pharmacological Intervention ◽  
Neutrophil Accumulation ◽  
Drug Induced

Acetaminophen (APAP) poisoning is one of the leading causes of acute hepatic failure and liver transplantation is often the only lifesaving alternative. During the course of hepatocyte necrosis, an intense accumulation of neutrophils is often observed within the liver microenvironment. Despite the classic idea that neutrophil accumulation in tissues causes collateral tissue damage, there is a growing body of evidence showing that neutrophils can also orchestrate the resolution of inflammation. In this work, drug-induced liver injury was induced by oral administration of APAP and pharmacological intervention was made 12 h after this challenge. Liver injury and repair kinetics were evaluated by a novel combination of enzyme quantifications, ELISA, specific antagonists of neutrophil enzymes and confocal intravital microscopy. We have demonstrated that neutrophil infiltration is not only involved in injury amplification, but also in liver tissue repair after APAP-induced liver injury. In fact, while neutrophil depletion led to reduced hepatic necrosis during APAP poisoning, injury recovery was also delayed in neutropenic mice. The mechanisms underlying the neutrophil reparative role involved rapid degranulation and matrix metalloproteinases (MMPs) activity. Our data highlights the crucial role of neutrophils, in particular for MMPs, in the resolution phase of APAP-induced inflammatory response.

Modulation of oxidative–nitrosative stress and inflammatory response by rapamycin in target and distant organs in rats exposed to hindlimb ischemia–reperfusion: the role of mammalian target of rapamycin

2019 ◽  
Vol 97 (12) ◽  
pp. 1193-1203
Author(s):  
Zumrut Kocak ◽  
Meryem Temiz-Resitoglu ◽  
Demet Sinem Guden ◽  
Ozden Vezir ◽  
Nehir Sucu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Signaling Pathway ◽  
Inducible Nitric Oxide Synthase ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion ◽  
Mammalian Target Of Rapamycin ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Mammalian target of rapamycin (mTOR) has been recognized with potential immunomodulatory properties playing an important role in various physiopathological processes including ischemia–reperfusion (I/R) injury. I/R injury stimulate reactive oxygen and nitrogen species by activating nicotinamide adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase, respectively. Controversial results have been obtained in different I/R models following localized I/R; however, the precise role of the mTOR signaling pathway remains undefined. The objective of the current study was to evaluate the role of the mTOR in oxidative–nitrosative stress and inflammation in hindlimb I/R-induced injury in target and remote organ injuries. In rats subjected to I/R, an increased expression of ribosomal protein S6 (rpS6), inhibitor κB (IκB)-α, nuclear factor-κB (NF-κB) p65, inducible nitric oxide synthase, cyclooxygenase 2, gp91phox, and levels of tumor necrosis factor α, nitrite, nitrotyrosine, malondialdehyde and the activities of myeloperoxidase and catalase in the tissues and (or) sera were detected. Treatment with rapamycin, a selective inhibitor of mTOR, reversed all the I/R-induced changes as manifested by its anti-inflammatory and antioxidant effects in kidney and gastrocnemius muscle of rats. Collectively, these findings suggest that rapamycin protects against I/R-induced oxidative–nitrosative stress and inflammation leading to organ injuries via suppression of mTOR/IκB-α/NF-κB signaling pathway.

scholarly journals Influence between NO and CO in guinea pig stomach fundus

Pharmacia ◽  
2020 ◽  
Vol 67 (3) ◽  
pp. 161-168
Author(s):  
Boris Kadinov ◽  
Dimitar Itzev
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Positive Staining ◽  
Stomach Fundus ◽  
Guinea Pig Stomach ◽  
Oxide Synthase

The interaction between carbon monoxide and nitric oxide and their role in modulation of stomach fundus excitability was studied. The presence and colocalization of heme oxygenase 1 (HO-1) and nitric oxide synthase (NOS) was verified in myentheric ganglia by immunohistochemistry. The role of inducible heme oxygenase isoenzyme was investigated after in vivo treatment of animals with CoCl2 (80 mg kg-1 b.w.) injected subcutaneously 24 hours before euthanasia. This treatment resulted in positive staining for the inducible isoform in stomach smooth muscle.

Neuroinflammation and demyelination from the point of nitrosative stress as a new target for neuroprotection

2015 ◽  
Vol 26 (1) ◽  
Author(s):  
Srdjan Ljubisavljevic ◽  
Ivana Stojanovic
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Experimental Studies ◽  
Protective Role ◽  
Clinical Effects ◽  
Inos Inhibitor ◽  
Potential Mode ◽  
Oxidative Processes ◽  
Oxide Synthase

AbstractThe role of nitrosative stress in the early pathogenesis of neuroinflammation and demyelination is undoubtedly wide. This review summarizes and integrates the results, found in previously performed studies, which have evaluated nitrosative stress participation in neuroinflammation. The largest number of studies indicates that the supply of nitrosative stress inhibitors has led to the opposite clinical effects in experimental studies. Some results claim that attributing the protective role to nitric oxide, outside the total changes of redox oxidative processes and without following the clinical and paraclinical correlates of neuroinflammation, is an overrated role of this mediator. The fact is that the use of nitrosative stress inhibitors would be justified in the earlier phases of neuroinflammation. The ideal choice would be a specific inducible nitric oxide synthase (iNOS) inhibitor, because its use would preserve the physiological features of nitric oxide produced by the effects of constitutive NOS. This review discusses the antinitrosative therapy as a potential mode of therapy that aims to control neuroinflammation in early phases, delaying its later phases, which are accompanied with irreversible neurological disabilities. Some parameters of nitrosative stress might serve as surrogate biomarkers for neuroinflammation intensity and its radiological and clinical correlates.

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