scholarly journals l-Arginine Availability Modulates Local Nitric Oxide Production and Parasite Killing in Experimental Trypanosomiasis

2000 ◽  
Vol 68 (8) ◽  
pp. 4653-4657 ◽  
Author(s):  
Alain P. Gobert ◽  
Sylvie Daulouede ◽  
Michel Lepoivre ◽  
Jean Luc Boucher ◽  
Bernard Bouteille ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Peritoneal Macrophages ◽  
No Production ◽  
Nitrite Production ◽  
Common Substrate ◽  
Nos Inhibitor

ABSTRACT Nitric oxide (NO) is an important effector molecule of the immune system in eliminating numerous pathogens. Peritoneal macrophages fromTrypanosoma brucei brucei-infected mice express type II NO synthase (NOS-II), produce NO, and kill parasites in the presence ofl-arginine in vitro. Nevertheless, parasites proliferate in the vicinity of these macrophages in vivo. The present study shows thatl-arginine availability modulates NO production. Trypanosomes use l-arginine for polyamine synthesis, required for DNA and trypanothione synthesis. Moreover, arginase activity is up-regulated in macrophages from infected mice from the first days of infection. Arginase competes with NOS-II for their common substrate, l-arginine. In vitro, arginase inhibitors decreased urea production, increased macrophage nitrite production, and restored trypanosome killing. In vivo, a dramatic decrease inl-arginine concentration was observed in plasma from infected mice. In situ restoration of NO production and trypanosome killing were observed when excess l-arginine, but notd-arginine or l-arginine plusN ω-nitro-l-arginine (a NOS inhibitor), was injected into the peritoneum of infected mice. These data indicate the role of l-arginine depletion, induced by arginase and parasites, in modulating the l-arginine–NO pathway under pathophysiological conditions.

Effect of Peganum Harmala Seeds Extract on Nitric Oxide in U937 Monocytes and Macrophages

2020 ◽  
Author(s):  
Nima Rahmati ◽  
Fatemeh Hajighasemi
Keyword(s):  
Nitric Oxide ◽  
Aqueous Extract ◽  
Calf Serum ◽  
Peritoneal Macrophages ◽  
No Production ◽  
Peganum Harmala ◽  
Logarithmic Growth Phase ◽  
Anti Inflammatory

Background and Aims: Nitric oxide (NO) has an essential role in inflammation and has been related to pathogenesis and the progress of numerous inflammatory-based diseases, including some cancers. Peganum harmala (P. harmala) is a medicinal plant used for the treatment of numerous diseases such as several infections. Also, anti-inflammatory effects of P. harmala extracts and its derivatives (harmaline and harmine) by suppressing myeloperoxidase, NO, and other mediators have been demonstrated in vivo. In this study, the effect of P. harmala seeds aqueous extract on NO production in U937 monocytic cells and peritoneal macrophages has been evaluated in vitro. Materials and Methods: U937 and mice peritoneal macrophages were cultured in Roswell Park Memorial institute-1640 with 10% fetal calf serum. Then, the cells at the logarithmic growth phase were incubated with different concentrations of aqueous extract of P. harmala seeds (0.1-1 mg/ml) for 24 hours. Next, NO production was assessed by the Griess method in the culture medium. Results: P. harmala seeds aqueous extract did not significantly affect lipopolysaccharide-induced NO production in U937 cells and peritoneal macrophages after 24 hours incubation time compared with untreated control cells. Conclusion: These results suggest that the anti-inflammatory effects of P. harmala may be mediated through NO-independent mechanism(s). However, further studies are warranted to define the P. harmala aqueous extract impact on NO expression in other related normal and cancerous cells.

scholarly journals Involvement of Nitric Oxide in Iodine Deficiency-Induced Microvascular Remodeling in the Thyroid Gland: Role of Nitric Oxide Synthase 3 and Ryanodine Receptors

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 707-720 ◽  
Author(s):  
J. Craps ◽  
C. Wilvers ◽  
V. Joris ◽  
B. De Jongh ◽  
J. Vanderstraeten ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Thyroid Gland ◽  
Mrna Expression ◽  
Iodine Deficiency ◽  
Ryanodine Receptors ◽  
No Production

Iodine deficiency (ID) induces microvascular changes in the thyroid gland via a TSH-independent reactive oxygen species-hypoxia inducible factor (HIF)-1α-vascular endothelial growth factor (VEGF) pathway. The involvement of nitric oxide (NO) in this pathway and the role of calcium (Ca2+) and of ryanodine receptors (RYRs) in NO synthase 3 (NOS3) activation were investigated in a murine model of goitrogenesis and in 3 in vitro models of ID, including primary cultures of human thyrocytes. ID activated NOS3 and the production of NO in thyrocytes in vitro and increased the thyroid blood flow in vivo. Using bevacizumab (a blocking antibody against VEGF-A) in mice, it appeared that NOS3 is activated upstream of VEGF-A. L-nitroarginine methyl ester (a NOS inhibitor) blocked the ID-induced increase in thyroid blood flow in vivo and NO production in vitro, as well as ID-induced VEGF-A mRNA and HIF-1α expression in vitro, whereas S-nitroso-acetyl-penicillamine (a NO donor) did the opposite. Ca2+ is involved in this pathway as intracellular Ca2+ flux increased after ID, and thapsigargin activated NOS3 and increased VEGF-A mRNA expression. Two of the 3 known mammalian RYR isoforms (RYR1 and RYR2) were shown to be expressed in thyrocytes. RYR inhibition using ryanodine at 10μM decreased ID-induced NOS3 activation, HIF-1α, and VEGF-A expression, whereas RYR activation with ryanodine at 1nM increased NOS3 activation and VEGF-A mRNA expression. In conclusion, during the early phase of TSH-independent ID-induced microvascular activation, ID sequentially activates RYRs and NOS3, thereby supporting ID-induced activation of the NO/HIF-1α/VEGF-A pathway in thyrocytes.

scholarly journals Endotoxin-induced skeletal muscle contractile dysfunction: contribution of nitric oxide synthases

1998 ◽  
Vol 274 (3) ◽  
pp. C770-C779 ◽  
Author(s):  
Q. El-Dwairi ◽  
A. Comtois ◽  
Y. Guo ◽  
S. N. A. Hussain
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
No Production ◽  
Contractile Dysfunction ◽  
Nos Inhibitor ◽  
Nos Isoforms ◽  
Muscle Contractile ◽  
Inducible Nos

The aims of this study were to assess the role of nitric oxide (NO) and the contribution of different NO synthase (NOS) isoforms in skeletal muscle contractile dysfunction in septic shock. Four groups of conscious rats were examined. Group 1 served as control; groups 2, 3, and 4 were injected with Escherichia coli endotoxin [lipopolysaccharide (LPS), 20 mg/kg ip] and killed after 6, 12, and 24 h, respectively. Protein expression was assessed by immunoblotting and immunostaining. LPS injection elicited a transient expression of the inducible NOS isoform, which peaked 12 h after LPS injection and disappeared within 24 h. This expression coincided with a significant increase in nitrotyrosine formation (peroxynitrite footprint). Muscle expression of the endothelial and neuronal NOS isoforms, by comparison, rose significantly and remained higher than control levels 24 h after LPS injection. In vitro measurement of muscle contractility 24 h after LPS injection showed that incubation with NOS inhibitor ( S-methyliosothiourea) restored the decline in submaximal force generation, whereas maximal muscle force remained unaffected. We conclude that NO plays a significant role in muscle contractile dysfunction in septic animals and that increased NO production is due to induction of the inducible NOS isoform and upregulation of constitutive NOS isoforms.

scholarly journals Clinical and Serologic Manifestations of Autoimmune Disease in MRL-lpr/lpr Mice Lacking Nitric Oxide Synthase Type 2

1997 ◽  
Vol 186 (3) ◽  
pp. 365-373 ◽  
Author(s):  
Gary S. Gilkeson ◽  
John S. Mudgett ◽  
Michael F. Seldin ◽  
Phil Ruiz ◽  
Audrey A. Alexander ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Immunoblot Analysis ◽  
Peritoneal Macrophages ◽  
No Production ◽  
Renal Vessels ◽  
Dna Antibodies ◽  
Nos Inhibitor ◽  
Oxide Synthase

Nitric oxide (NO) is an important mediator of the inflammatory response. MRL–lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manifestations. In previous studies, we showed that inhibiting NO production with the nonselective nitric oxide synthase (NOS) inhibitor NG-monomethyl–arginine reduced glomerulonephritis, arthritis, and vasculitis in MRL–lpr/lpr mice. To define further the role of NO and NOS2 in disease in MRL–lpr/lpr mice, mice with targeted disruption of NOS2 were produced by homologous recombination and bred to MRL–lpr/lpr mice to the N4 generation. MRL–lpr/lpr littermates homozygous for disrupted NOS2 (−/−), heterozygous for disrupted NOS2 (+/−), or wildtype (+/+) were derived for this study. Measures of NO production were markedly decreased in the MRL-lpr/lpr (−/−) mice compared with MRL-lpr/lpr (+/+) mice, with intermediate production by the MRL-lpr/lpr (+/−) mice. There was no detectable NOS2 protein by immunoblot analysis of the spleen, liver, kidney, and peritoneal macrophages of the (−/−) animals, whereas that of (+/+) was high and (+/−) intermediate. The (−/−) mice developed glomerular and synovial pathology similar to that of the (+/−) and (+/+) mice. However, (−/−) mice and (+/−) mice had significantly less vasculitis of medium-sized renal vessels than (+/+) mice. IgG rheumatoid factor levels were significantly lower in the (−/−) mice as compared with (+/+) mice, but levels of anti-DNA antibodies were comparable in all groups. Our findings show that NO derived from NOS2 has a variable impact on disease manifestations in MRL-lpr/lpr mice, suggesting heterogeneity in disease mechanisms.

scholarly journals Phaseolin Attenuates Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells and Zebrafish

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 420
Author(s):  
Su-Jung Hwang ◽  
Ye-Seul Song ◽  
Hyo-Jong Lee
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Raw 264.7 Cells ◽  
Network Pharmacology ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Bioactive Constituents

Kushen (Radix Sophorae flavescentis) is used to treat ulcerative colitis, tumors, and pruritus. Recently, phaseolin, formononetin, matrine, luteolin, and quercetin, through a network pharmacology approach, were tentatively identified as five bioactive constituents responsible for the anti-inflammatory effects of S. flavescentis. However, the role of phaseolin (one of the primary components of S. flavescentis) in the direct regulation of inflammation and inflammatory processes is not well known. In this study, the beneficial role of phaseolin against inflammation was explored in lipopolysaccharide (LPS)-induced inflammation models of RAW 264.7 macrophages and zebrafish larvae. Phaseolin inhibited LPS-mediated production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), without affecting cell viability. In addition, phaseolin suppressed pro-inflammatory mediators such as cyclooxygenase 2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in a dose-dependent manner. Furthermore, phaseolin reduced matrix metalloproteinase (MMP) activity as well as macrophage adhesion in vitro and the recruitment of leukocytes in vivo by downregulating Ninjurin 1 (Ninj1), an adhesion molecule. Finally, phaseolin inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB). In view of the above, our results suggest that phaseolin could be a potential therapeutic candidate for the management of inflammation.

scholarly journals Novel Insights on the Role of Nitric Oxide in the Ovary: A Review of the Literature

2021 ◽  
Vol 18 (3) ◽  
pp. 980
Author(s):  
Maria Cristina Budani ◽  
Gian Mario Tiboni
Keyword(s):  
Nitric Oxide ◽  
In Vivo Studies ◽  
Published Data ◽  
Vitro Fertilization ◽  
Peripheral Neurons ◽  
Relevant Role ◽  
Oocyte Meiotic Maturation

Nitric oxide (NO) is formed during the oxidation of L-arginine to L-citrulline by the action of multiple isoenzymes of NO synthase (NOS): neuronal NOS (nNOS), endotelial NOS (eNOS), and inducible NOS (iNOS). NO plays a relevant role in the vascular endothelium, in central and peripheral neurons, and in immunity and inflammatory systems. In addition, several authors showed a consistent contribution of NO to different aspects of the reproductive physiology. The aim of the present review is to analyse the published data on the role of NO within the ovary. It has been demonstrated that the multiple isoenzymes of NOS are expressed and localized in the ovary of different species. More to the point, a consistent role was ascribed to NO in the processes of steroidogenesis, folliculogenesis, and oocyte meiotic maturation in in vitro and in vivo studies using animal models. Unfortunately, there are few nitric oxide data for humans; there are preliminary data on the implication of nitric oxide for oocyte/embryo quality and in-vitro fertilization/embryo transfer (IVF/ET) parameters. NO plays a remarkable role in the ovary, but more investigation is needed, in particular in the context of human ovarian physiology.

scholarly journals Effects of chitosan on nitric oxide production and inducible nitric oxide synthase activity and mRNA expression in weaned piglets

2018 ◽  
Vol 60 (No. 8) ◽  
pp. 359-366
Author(s):  
J. Li ◽  
B. Shi ◽  
S. Yan ◽  
L. Jin ◽  
Y. Guo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Inducible Nitric Oxide Synthase ◽  
No Production ◽  
Weaned Piglets ◽  
Inos Activity ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The effects of chitosan on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity and gene expression in vivo or vitro were investigated in weaned piglets. In vivo, 180 weaned piglets were assigned to five dietary treatments with six replicates. The piglets were fed on a basal diet supplemented with 0 (control), 100, 500, 1000, and 2000 mg chitosan/kg feed, respectively. In vitro, the peripheral blood mononuclear cells (PBMCs) from a weaned piglet were cultured respectively with 0 (control), 40, 80, 160, and 320 µg chitosan/ml medium. Results showed that serum NO concentrations on days 14 and 28 and iNOS activity on day 28 were quadratically improved with increasing chitosan dose (P < 0.05). The iNOS mRNA expressions were linearly or quadratically enhanced in the duodenum on day 28, and were improved quadratically in the jejunum on days 14 and 28 and in the ileum on day 28 (P < 0.01). In vitro, the NO concentrations, iNOS activity, and mRNA expression in unstimulated PBMCs were quadratically enhanced by chitosan, but the improvement of NO concentrations and iNOS activity by chitosan were markedly inhibited by N-(3-[aminomethyl] benzyl) acetamidine (1400w) (P < 0.05). Moreover, the increase of NO concentrations, iNOS activity, and mRNA expression in PBMCs induced by lipopolysaccharide (LPS) were suppressed significantly by chitosan (P < 0.05). The results indicated that the NO concentrations, iNOS activity, and mRNA expression in piglets were increased by feeding chitosan in a dose-dependent manner. In addition, chitosan improved the NO production in unstimulated PBMCs but inhibited its production in LPS-induced cells, which exerted bidirectional regulatory effects on the NO production via modulated iNOS activity and mRNA expression.

scholarly journals Role of nitric oxide in heparin-induced attenuation of hypoxic pulmonary vascular remodeling

2002 ◽  
Vol 92 (5) ◽  
pp. 2012-2018 ◽  
Author(s):  
Damian J. Horstman ◽  
Lars G. Fischer ◽  
Peter C. Kouretas ◽  
Robert L. Hannan ◽  
George F. Rich
Keyword(s):  
Nitric Oxide ◽  
Vascular Remodeling ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Remodeling ◽  
Antiproliferative Effects ◽  
Coculture Model ◽  
Pulmonary Arterial ◽  
Nos Inhibitor

Heparin and nitric oxide (NO) attenuate changes to the pulmonary vasculature caused by prolonged hypoxia. Heparin may increase NO; therefore, we hypothesized that heparin may attenuate hypoxia-induced pulmonary vascular remodeling via a NO-mediated mechanism. In vivo, rats were exposed to normoxia (N) or hypoxia (H; 10% O2) with or without heparin (1,200 U · kg−1 · day−1) and/or the NO synthase (NOS) inhibitor N ω-nitro-l-arginine methyl ester (l-NAME; 20 mg · kg−1 · day−1) for 3 days or 3 wk. Heparin attenuated increases in pulmonary arterial pressure, the percentage of muscular pulmonary vessels, and their medial thickness induced by 3 wk of H. Importantly, althoughl-NAME alone had no effect, it prevented these effects of heparin on vascular remodeling. In H lungs, heparin increased NOS activity and cGMP levels at 3 days and 3 wk and endothelial NOS protein expression at 3 days but not at 3 wk. In vitro, heparin (10 and 100 U · kg−1 · ml−1) increased cGMP levels after 10 min and 24 h in N and anoxic (0% O2) endothelial cell-smooth muscle cell (SMC) coculture. SMC proliferation, assessed by 5-bromo-2′-deoxyuridine incorporation during a 3-h incubation period, was decreased by heparin under N, but not anoxic, conditions. The antiproliferative effects of heparin were not altered byl-NAME. In conclusion, the in vivo results suggest that attenuation of hypoxia-induced pulmonary vascular remodeling by heparin is NO mediated. Heparin increases cGMP in vitro; however, the heparin-induced decrease in SMC proliferation in the coculture model appears to be NO independent.

scholarly journals In Vitro Study of Nitric Oxide Metabolites Effects on Human Hydatid ofEchinococcus granulosus

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Razika Zeghir-Bouteldja ◽  
Manel Amri ◽  
Saliha Aitaissa ◽  
Samia Bouaziz ◽  
Dalila Mezioug ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hydatid Cyst ◽  
Echinococcus Granulosus ◽  
In Vitro Study ◽  
No Production ◽  
In Vitro Effects ◽  
Nitric Oxide Metabolites

Hydatidosis is characterized by the long-term coexistence of larvaEchinococcus granulosusand its host without effective rejection. Previous studies demonstrated nitric oxide (NO) production (in vivo and in vitro) during hydatidosis. In this study, we investigated the direct in vitro effects of NO species: nitrite (NO2−), nitrate (NO3−) and peroxynitrite (ONOO−) on protoscolices (PSCs) viability and hydatid cyst layers integrity for 24 hours and 48 hours. Our results showed protoscolicidal activity ofNO2−andONOO−24 hours and 3 hours after treatment with 320 μM and 80 μM respectively. Degenerative effects were observed on germinal and laminated layers. The comparison of the in vitro effects of NO species on the PSCs viability indicated thatONOO−is more cytotoxic thanNO2−. In contrast,NO3−has no effect. These results suggest possible involvement ofNO2−andONOO−in antihydatic action and point the efficacy of these metabolites as scolicidal agents.

Losartan Increases No Production from the Bovine Aortic Wall That is Stimulated by Angiotensin II

2003 ◽  
Vol 1 (3) ◽  
pp. 113-117 ◽  
Author(s):  
M. Myronidou ◽  
B. Kokkas ◽  
A. Kouyoumtzis ◽  
N. Gregoriadis ◽  
A. Lourbopoulos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Aortic Wall ◽  
Vascular Wall ◽  
Protective Role ◽  
Normal Function ◽  
No Production ◽  
Chemical Inactivation

In these studies we investigated if losartan, an AT1- receptor blocker has any beneficial effect on NO production from the bovine aortic preparations in vitro while under stimulation from angiotensin II. Experiments were performed on intact specimens of bovine thoracic aorta, incubated in Dulbeco's MOD medium in a metabolic shaker for 24 hours under 95 % O2 and 5 % CO2 at a temperature of 37°C. We found that angiotensin II 1nM−10 μM does not exert any statistically significant action on NO production. On the contrary, angiotensin II 10nM increases the production of NO by 58.14 % (from 12.16 + 2.9 μm/l to 19.23 + 4.2 μm/l in the presence of losartan 1nM (P<0.05). Nitric oxide levels depend on both rate production and rate catabolism or chemical inactivation. Such an equilibrium is vital for the normal function of many systems including the cardiovascular one. The above results demonstrate that the blockade of AT1-receptors favors the biosynthesis of NO and indicate the protective role of losartan on the vascular wall.

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