scholarly journals Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Iva Bozic ◽  
Danijela Savic ◽  
Marija Jovanovic ◽  
Ivana Bjelobaba ◽  
Danijela Laketa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Low Dose ◽  
Nitrosative Stress ◽  
Morphological Changes ◽  
Necrosis Factor Alpha ◽  
External Threats ◽  
Cytokine Tumor Necrosis Factor ◽  
Induced Apoptosis ◽  
Oxide Synthase

Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM) modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM) to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS) stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation.

scholarly journals Inducible Nitric Oxide Synthase Is Not Essential for Control of Trypanosoma cruzi Infection in Mice

2004 ◽  
Vol 72 (7) ◽  
pp. 4081-4089 ◽  
Author(s):  
Kara L. Cummings ◽  
Rick L. Tarleton
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Trypanosoma Cruzi ◽  
Inducible Nitric Oxide Synthase ◽  
Interleukin 1 ◽  
Mouse Strains ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Immune control of many intracellular pathogens, including Trypanosoma cruzi, is reported to be dependent on the production of nitric oxide. In this study, we show that mice deficient in inducible nitric oxide synthase (iNOS or NOS2) exhibit resistance to T. cruzi infection that is comparable to that of wild-type mice. This is the case for two iNOS-deficient mouse strains, Nos2tm1Lau and Nos2 N5, infected with the Brazil or Tulahuen strain of T. cruzi. In all cases, blood parasitemia, tissue parasite load, and survival rates are similar between wild-type and iNOS-deficient mice. In contrast, both wild-type and Nos2tm1Lau mice died within 32 days postinfection when treated with the nitric oxide synthase inhibitor aminoguanidine. Increased transcription of NOS1 or NOS3 is not found in iNOS-knockout (KO) mice, indicating that the absence of nitric oxide production through iNOS is not compensated for by increased production of other NOS isoforms. However, Nos2tm1Lau mice exhibit enhanced expression of tumor necrosis factor alpha, interleukin-1, and macrophage inflammatory protein 1α compared to that of wild-type mice, and these alterations may in part compensate for the lack of iNOS. These results clearly show that iNOS is not required for control of T. cruzi infection in mice.

Activation of nitric oxide synthase is involved in tamoxifen-induced apoptosis of human erythroleukemia K562 cells

FEBS Letters ◽  
1998 ◽  
Vol 434 (3) ◽  
pp. 421-424 ◽  
Author(s):  
Mauro Maccarrone ◽  
Cristina Fantini ◽  
Marco Ranalli ◽  
Gerry Melino ◽  
Alessandro Finazzi Agrò
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
K562 Cells ◽  
Induced Apoptosis ◽  
Oxide Synthase

Nitric oxide is involved in ischemia-induced apoptosis in brain: a study in neuronal nitric oxide synthase null mice

Neuroscience ◽  
2001 ◽  
Vol 105 (1) ◽  
pp. 79-86 ◽  
Author(s):  
B Elibol ◽  
F Söylemezoglu ◽  
I Ünal ◽  
M Fujii ◽  
L Hirt ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Induced Apoptosis ◽  
Oxide Synthase

scholarly journals Expression of the Nitric Oxide Synthase 2 Gene Is Not Essential for Early Control of Mycobacterium tuberculosis in the Murine Lung

2000 ◽  
Vol 68 (12) ◽  
pp. 6879-6882 ◽  
Author(s):  
Andrea M. Cooper ◽  
John E. Pearl ◽  
Jason V. Brooks ◽  
Stefan Ehlers ◽  
Ian M. Orme
Keyword(s):  
Nitric Oxide ◽  
Mycobacterium Tuberculosis ◽  
Nitric Oxide Synthase ◽  
Low Dose ◽  
Interleukin 12 ◽  
Infection Model ◽  
Rapid Progression ◽  
Ifn Γ ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase

ABSTRACT The interleukin-12 and gamma interferon (IFN-γ) pathway of macrophage activation plays a pivotal role in controlling tuberculosis. In the murine model, the generation of supplementary nitric oxide by the induction of the nitric oxide synthase 2 (NOS2) gene product is considered the principal antimicrobial mechanism of IFN-γ-activated macrophages. Using a low-dose aerosol-mediated infection model in the mouse, we have investigated the role of nitric oxide in controllingMycobacterium tuberculosis in the lung. In contrast to the consequences of a systemic infection, a low dose of bacteria introduced directly into the lungs of mice lacking the NOS2 gene is controlled almost as well as in intact animals. This is in contrast to the rapid progression of disease in mice lacking IFN-γ or a key member of the IFN signaling pathway, interferon regulatory factor 1. Thus while IFN-γ is pivotal in early control of bacterial growth in the lung, this control does not completely depend upon the expression of the NOS2 gene. The absence of inducible nitric oxide in the lung does, however, result in increased polymorphonuclear cell involvement and eventual necrosis in the pulmonary granulomas of the infected mice lacking the NOS2 gene.

Stimulation of the endogenous hydrogen sulfide synthesis suppresses oxidative–nitrosative stress and restores endothelial-dependent vasorelaxation in old rats

2020 ◽  
Vol 98 (5) ◽  
pp. 275-281 ◽  
Author(s):  
L.A. Mys ◽  
N.A. Strutynska ◽  
Y.V. Goshovska ◽  
V.F. Sagach
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Nitric Oxide Synthase ◽  
Vascular Reactivity ◽  
Nitrosative Stress ◽  
Rat Aorta ◽  
Aortic Tissue ◽  
Old Rats ◽  
Oxide Synthase ◽  
Stimulation Of

Hydrogen sulfide (H2S) is an endogenous gas transmitter with profound effects on the cardiovascular system. We hypothesized that stimulation of H2S synthesis might alleviate age-associated changes in vascular reactivity. Pyridoxal-5-phosphate (PLP), the coenzyme of H2S-synthesizing enzymes, was administrated to old male Wistar rats per os at a dose of 0.7 mg/kg body mass once a day for 2 weeks. H2S content in the aortic tissue, markers of oxidative stress, inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS), arginase activities, and endothelium-dependent vasorelaxation of the aortic rings were studied. Our results showed that PLP restored endogenous H2S and low molecular weight S-nitrosothiol levels in old rat aorta to the levels detected in adults. PLP significantly reduced diene conjugate content, hydrogen peroxide and peroxynitrite generation rates, and iNOS and arginase activity in the aortic tissue of old rats. PLP also greatly improved acetylcholine-induced relaxation of old rat aorta (47.7% ± 4.8% versus 18.4% ± 4.1% in old rats, P < 0.05) that was abolished by NO inhibition with N-nitro-l-arginine methyl ester hydrochloride (L-NAME) or H2S inhibition with O-carboxymethylhydroxylamine (O-CMH). Thus, PLP might be used for stimulation of endogenous H2S synthesis and correction of oxidative and nitrosative stress and vessel tone dysfunction in aging and age-associated diseases.

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