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.

scholarly journals Role of nitric oxide in hepatic microvascular injury elicited by acetaminophen in mice

2004 ◽  
Vol 286 (1) ◽  
pp. G60-G67 ◽  
Author(s):  
Yoshiya Ito ◽  
Edward R. Abril ◽  
Nancy W. Bethea ◽  
Robert S. McCuskey
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
Cell Injury ◽  
Parenchymal Cell ◽  
Protective Role ◽  
Hepatic Expression ◽  
Inos Inhibitor ◽  
Microcirculatory Disturbances

Nitric oxide (NO) is suggested to play a role in liver injury elicited by acetaminophen (APAP). Hepatic microcirculatory dysfunction also is reported to contribute to the development of the injury. As a result, the role of NO in hepatic microcirculatory alterations in response to APAP was examined in mice by in vivo microscopy. A selective inducible NO synthase (iNOS) inhibitor,l- N6-(1-iminoethyl)-lysine (l-NIL), or a nonselective NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), was intraperitoneally administered to animals 10 min before APAP gavage. l-NIL suppressed raised alanine aminotransferase (ALT) values 6 h after APAP, whereas l-NAME increased those 1.7-fold. Increased ALT levels were associated with hepatic expression of iNOS. l-NIL, but not l-NAME, reduced the expression. APAP caused a reduction (20%) in the numbers of perfused sinusoids. l-NIL restored the sinusoidal perfusion, but l-NAME was ineffective. APAP increased the area occupied by infiltrated erythrocytes into the extrasinusoidal space. l-NIL tended to minimize this infiltration, whereas l-NAME further enhanced it. APAP caused an increase (1.5-fold) in Kupffer cell phagocytic activity. This activity in response to APAP was blunted by l-NIL, whereas l-NAME further elevated it. l-NIL suppressed APAP-induced decreases in hepatic glutathione levels. These results suggest that NO derived from iNOS contributes to APAP-induced parenchymal cell injury and hepatic microcirculatory disturbances. l-NIL exerts preventive effects on the liver injury partly by inhibiting APAP bioactivation. In contrast, NO derived from constitutive isoforms of NOS exerts a protective role in liver microcirculation against APAP intoxication and thereby minimizes liver injury.

Protective Role of the L-Arginine-Nitric Oxide Synthase Pathway on Preservation Injury after Rat Liver Transplantation

2001 ◽  
Vol 25 (3) ◽  
pp. 142-147 ◽  
Author(s):  
David A. Geller ◽  
Stanley H. Chia ◽  
Yoshihito Takahashi ◽  
Gautam P. Yagnik ◽  
George Tsoulfas ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Transplantation ◽  
Nitric Oxide Synthase ◽  
Rat Liver ◽  
Protective Role ◽  
Rat Liver Transplantation ◽  
Preservation Injury ◽  
Oxide Synthase

scholarly journals The Protective Role of Bacillus Anthracis Exosporium in Macrophage-Mediated Killing by Nitric Oxide

2007 ◽  
Author(s):  
John Weaver ◽  
Tae Jin Kang ◽  
Kimberly Raines ◽  
Guan-Liang Cao ◽  
Stephen Hibbs ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bacillus Anthracis ◽  
Protective Role ◽  
Oxygen Species ◽  
Activated Macrophages ◽  
Positive Bacterium ◽  
Bacterium Bacillus ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis to survive exposure to antibacterial killing mechanisms by activated macrophages is key to its germination and survival. These antibacterial killing mechanisms include, but are not limited to the generation of free radicals such as nitric oxide (•NO) and superoxide (O2•−) from the upregulation of inducible nitric oxide synthase (NOS 2) along with products derived from them, e.g., peroxynitrite (ONOO−), as part of microbicidal activity. However questions still remain as to how these species are involved in microbial killing, specifically with respect to B. anthracis. In a previous study, we demonstrated that exposure of primary murine macrophages to sonicated B. anthracis endospores up-regulated NOS 2 and demonstrated a •NO-dependent bactericidal response, but unanswered in that study was which of the NOS 2-derived reactive oxygen species was responsible for the observed bactericidal response. Since NOS 2 also generates O2•−, experiments were designed to determine whether NOS 2 formed ONOO− from the reaction of •NO with O2•− and if so, was ONOO− microbicidal toward B. anthracis.

Protective role of nitric oxide synthase against ischemia-reperfusion injury in guinea pig myocardial mitochondria

1999 ◽  
Vol 380 (1) ◽  
pp. 37-48 ◽  
Author(s):  
Yoshihiro Hotta ◽  
Hidetsugu Otsuka-Murakami ◽  
Michiko Fujita ◽  
Junichi Nakagawa ◽  
Michio Yajima ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Guinea Pig ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Myocardial Mitochondria ◽  
Oxide Synthase

scholarly journals Is there a role of inducible nitric oxide synthase activation in the delayed antiarrhythmic effect of sodium nitrite?

2017 ◽  
Vol 95 (4) ◽  
pp. 447-454 ◽  
Author(s):  
Vivien Demeter-Haludka ◽  
László Juhász ◽  
Mária Kovác ◽  
János Gardi ◽  
Ágnes Végh
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Sodium Nitrite ◽  
Antiarrhythmic Effect ◽  
Inos Inhibitor ◽  
Ectopic Beats ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

This study aimed to examine whether inducible nitric oxide synthase (iNOS) plays a role in the delayed antiarrhythmic effect of sodium nitrite. Twenty-one dogs were infused intravenously with sodium nitrite (0.2 μmol·kg–1·min–1) for 20 min, either in the absence (n = 12) or in the presence of the iNOS inhibitor S-(2-aminoethyl)-isothiourea (AEST) (total dose 2.0 mg·kg–1 i.v., n = 9). Control dogs (n = 12) were given saline. Twenty-four hours later, all of the dogs were subjected to a 25 min period occlusion of the left anterior descending coronary artery followed by rapid reperfusion. Dogs treated with AEST and nitrite received again AEST prior to the occlusion. Compared with the controls, sodium nitrite markedly reduced the number of ectopic beats, the number and incidence of ventricular tachycardia, and the incidence of ventricular fibrillation during occlusion and increased survival (0% versus 50%) from the combined ischaemia and reperfusion insult. Although AEST completely inhibited iNOS activity, the nitrite-induced increase in NO bioavailability during occlusion was not substantially modified. Furthermore, AEST attenuated but did not completely abolish the antiarrhythmic effect of nitrite. The marked delayed antiarrhythmic effect of sodium nitrite is not entirely due to the activation of iNOS; other mechanisms may certainly play a role.

scholarly journals The Inducible Nitric Oxide Synthase Locus Confers Protection against Aerogenic Challenge of Both Clinical and Laboratory Strains of Mycobacterium tuberculosis in Mice

2001 ◽  
Vol 69 (12) ◽  
pp. 7711-7717 ◽  
Author(s):  
Charles A. Scanga ◽  
Vellore P. Mohan ◽  
Kathryn Tanaka ◽  
David Alland ◽  
JoAnne L. Flynn ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mycobacterium Tuberculosis ◽  
Nitric Oxide Synthase ◽  
Protective Role ◽  
Clinical Isolates ◽  
Intravenous Route ◽  
Tuberculous Infection ◽  
Oxide Synthase

ABSTRACT Murine macrophages effect potent antimycobacterial function via the production of nitric oxide by the inducible isoform of the enzyme nitric oxide synthase (NOS2). The protective role of reactive nitrogen intermediates (RNI) against Mycobacterium tuberculosisinfection has been well established in various murine experimental tuberculosis models using laboratory strains of the tubercle bacillus to establish infection by the intravenous route. However, important questions remain about the in vivo importance of RNI in host defense against M. tuberculosis. There is some evidence that RNI play a lesser role following aerogenic, rather than intravenous,M. tuberculosis infection of mice. Furthermore, in vitro studies have demonstrated that different strains of M. tuberculosis, including clinical isolates, vary widely in their susceptibility to the antimycobacterial effects of RNI. Thus, we sought to test rigorously the protective role of RNI against infection with recent clinical isolates of M. tuberculosis following both aerogenic and intravenous challenges. Three recently isolated and unique M. tuberculosis strains were used to infect both wild-type (wt) C57BL/6 and NOS2 gene-disrupted mice. Regardless of the route of infection, NOS2−/− mice were much more susceptible than wt mice to any of the clinical isolates or to either the Erdman or H37Rv laboratory strain of M. tuberculosis. Mycobacteria replicated to much higher levels in the organs of NOS2−/− mice than in those of wt mice. Although the clinical isolates all exhibited enhanced virulence in NOS2−/− mice, they displayed distinct growth rates in vivo. The present study has provided results indicating that RNI are required for the control of murine tuberculous infection caused by both laboratory and clinical strains of M. tuberculosis. This protective role of RNI is essential for the control of infection established by either intravenous or aerogenic challenge.

scholarly journals Protective role of nitric oxide synthase in mitochondria against ischemia-reperfusion injury in guinea-pig hearts

1998 ◽  
Vol 76 ◽  
pp. 286
Author(s):  
Yoshihiro Hotta ◽  
Michiko Fujita ◽  
Junichi Nakagawa ◽  
Hidetugu Murakami ◽  
Michio Yajima ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Guinea Pig ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Oxide Synthase

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.

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