scholarly journals A Potential Concept In The Management of Tumors With Modulation of Prostaglandin, Nitric Oxide and Antioxidants

2007 ◽  
Vol 7 ◽  
pp. 466-478 ◽  
Author(s):  
Noori S. Al-Waili
Keyword(s):  
Nitric Oxide ◽  
Bone Marrow ◽  
Immune Cells ◽  
Serum Iron ◽  
No Production ◽  
Patients With Cancer ◽  
Colon Cancers ◽  
Bone Marrow Function ◽  
No Free Radicals

Prostaglandins (PGs), nitric oxide (NO), free radicals and chronic inflammation play a major role in tumorogenesis. We have foundin vivothat PGs suppress antibody production; reduce serum iron, and modulate bone marrow function. Tumors are associated with immunosuppression and anemia. We have hypothesized that the over-production of PGs is responsible for immunosuppression and anemia in conditions associated with increased production of PG such as tumor, and that PG inhibitors might help reversing immunosuppression and anemia, and play a role in eradication and prevention of tumors. This is supported by reports that demonstrate the immunosuppressive effects of PGs in tumors. PG inhibitors have also been shown to be crucial in the prevention of tumors such as esophageal and colon cancers. Others and we have found that high NO production was encountered in patients with cancer while antioxidants are decreased. Evidence supports the efficacy of PG inhibition in malignancies, and the concept of PG inhibition, NO modulation, anti-oxidants, immunotherapy with antibody or immune cells, and anti-inflammatory agents when used in the prevention and management of malignancies are discussed.

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 Simultaneous Assessment of Endothelial Function, Nitric Oxide Synthase Activity, Nitric Oxide–Mediated Signaling, and Oxidative Stress in Individuals with and without Hypercholesterolemia

2008 ◽  
Vol 54 (2) ◽  
pp. 292-300 ◽  
Author(s):  
Renke Maas ◽  
Edzard Schwedhelm ◽  
Lydia Kahl ◽  
Huige Li ◽  
Ralf Benndorf ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Urinary Excretion ◽  
Indirect Evidence ◽  
No Oxidation ◽  
Whole Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Synthesis Rate ◽  
No Production

Abstract Background: Endothelial function is impaired in hypercholesterolemia and atherosclerosis. Based on mostly indirect evidence, this impairment is attributed to reduced synthesis or impaired biological activity of endothelium-derived nitric oxide (NO). It was the aim of this study to directly estimate and compare whole-body NO production in normo- and hypercholesterolemia by applying a nonradioactive stable isotope dilution technique in vivo. Methods: We enrolled 12 normocholesterolemic and 24 hypercholesterolemic volunteers who were all clinically healthy. To assess whole-body NO synthesis, we intravenously administered l-[guanidino-(15N2)]-arginine and determined the urinary excretion of 15N-labeled nitrate, the specific end product of NO oxidation in humans, by use of gas chromatography-mass spectrometry. In addition, we measured flow-mediated vasodilation (FMD) of the brachial artery, expression of endothelial NOS (eNOS) in platelets, plasma concentration of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), and urinary excretion of 8-isoprostaglandin F2α (8-iso-PGF2α). Results: After infusion of l-[guanidino-(15N2)]-arginine, cumulative excretion of 15N-labeled-nitrate during 48 h was 40% [95% CI 15%–66%] lower in hypercholesterolemic than normocholesterolemic volunteers [mean 9.2 (SE 0.8) μmol vs 15.4 (2.3) μmol/l, P = 0.003]. FMD was on average 36% [4%–67%] lower in hypercholesterolemic than normocholesterolemic volunteers [6.3 (4.0)% vs 9.4 (4.6)%, P = 0.027]. Normalized expression of NOS protein in platelets was also significantly lower in hypercholesterolemic volunteers, whereas there were no significant differences in plasma ADMA concentration or urinary excretion of 8-iso-PGF2α between the 2 groups. Conclusions: This study provides direct evidence for a decreased whole body NO synthesis rate in healthy people with hypercholesterolemia.

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.

scholarly journals Candida albicans Activation of Human Monocytes Toward M2 Profile is Reversed by Amphotericin B and Fluconazole

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Icely PA ◽  
◽  
Vigezzi C ◽  
Rodriguez E ◽  
Miró MS ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Candida Albicans ◽  
Amphotericin B ◽  
Immune Cells ◽  
Fungal Growth ◽  
Antifungal Drugs ◽  
Arginase Activity ◽  
Intrinsic Activity ◽  
No Production ◽  
Human Monocytes

Phagocytes, including monocytes/macrophages, play an important role in the host defense during Candida albicans infections. In the L-arginine metabolism, the balance between the activation of two enzymes, inducible Nitric Oxide Synthase (iNOS) and arginase, promotes in the macrophages two alternative metabolic states, while M1 profile is related with host protection, M2 favored the fungal growth and evasion. Our aim was to evaluate the effect of Amphotericin B (AMB) and Fluconazole (FLC) on polarization of human monocytes to M2 profile induced by C. albicans. The human monocytic (Mo) cell line U937 was co-cultured with viable yeast of C. albicans, or Lipopolysaccharides (LPS) or Phorbol-12-myristate-13-acetate (PMA). Nitric Oxide (NO), cytokines production and arginase activity were evaluated. The effect of AMB or FLC on these metabolic pathways in immune cells and on fungus intrinsic arginase activity was studied. C. albicans inhibits NO production in human-monocyte and induces strong host arginase activity (p<0.0001). AMB and FLC inhibited C. albicansinduced arginase activity in immune cells (p<0.001), reaching a percentage of inhibition of 90% for AMB and 78% for FLC. Arginase intrinsic activity of the fungus was blocked by nor-NOHA (arginase inhibitor) and AMB (p<0.05). These results show that C. albicans drives human Mo toward M2 profile and that both antifungal drugs evaluated have the ability to revert C. albicans-induced M2 profile. In a relevant manner, it also provides data about additional effect of AMB as inhibitor of C. albicans endogenous arginase activity. Here in we provide new evidence for the effect of these drugs over the immune cells and the yeast.

scholarly journals NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

2021 ◽  
Author(s):  
Anuj K Yadav ◽  
Michael C. Lee ◽  
Melissa Lucero ◽  
Christopher J. Reinhardt ◽  
ShengZhang Su ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Critical Role ◽  
Cellular Systems ◽  
Tissue Imaging ◽  
Molecular Evidence ◽  
No Production ◽  
The Impact

<p>Nitric oxide (NO) plays a critical role in acute and chronic inflammation. NO’s contributions to cancer are of particular interest due to its context-dependent bioactivities. For example, immune cells initially produce cytotoxic quantities of NO in response to the nascent tumor. However, it is believed that this fades over time and reaches a concentration that supports the tumor microenvironment (TME). These complex dynamics are further complicated by other factors, such as diet and oxygenation, making it challenging to establish a complete picture of NO’s impact on tumor progression. Although many activity-based sensing (ABS) probes for NO have been developed, only a small fraction have been employed <i>in vivo </i>and fewer yet are practical in cancer models where the NO concentration is < 200 nM. To overcome this outstanding challenge, we have developed BL<sub>660</sub>-NO, the first ABS probe for NIR bioluminescence imaging of NO in cancer. Owing to the low intrinsic background, high sensitivity, and deep tissue imaging capabilities of our design, BL<sub>660</sub>-NO was successfully employed to visualize endogenous NO in cellular systems, a human liver metastasis model, and a murine breast cancer model. Importantly, its exceptional performance facilitated the design of a dietary study to examine the impact of NO on the TME by varying the intake of fat. BL<sub>660</sub>-NO provides the first direct molecular evidence that intratumoral NO becomes elevated in mice fed a high-fat diet who became obese with larger tumors compared to control animals on a low-fat diet. These results indicate that an inflammatory diet can increase NO production via recruitment of macrophages and overexpression of iNOS which in turn can drive tumor progression.<br></p>

Nitric oxide limits coronary vasoconstriction by a shear stress-dependent mechanism

2001 ◽  
Vol 281 (2) ◽  
pp. H796-H803 ◽  
Author(s):  
David W. Stepp ◽  
Daphne Merkus ◽  
Yasuhiro Nishikawa ◽  
William M. Chilian
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Coronary Microcirculation ◽  
Shear Stresses ◽  
No Production ◽  
Small Arteries ◽  
Inner Diameter ◽  
Stress Dependent ◽  
Dependent Mechanism

Increases in shear stress promote coronary vasodilation by stimulating the production of nitric oxide (NO). Whether shear stress-induced NO production also limits vasoconstriction in the coronary microcirculation in vivo is unknown. Accordingly, we measured microvascular diameter and flow velocity in the beating heart along with estimated blood viscosity to calculate shear stress during vasoconstriction with endothelin or vasopressin. Measurements were repeated in the presence of N G-monomethyl-l-arginine (l-NMMA) to inhibit NO production and BQ-788 to block NO-linked endothelin type B receptors. BQ-788 did not augment steady-state constriction to endothelin, suggesting that NO production via activation of this receptor is inconsequential. l-NMMA potentiated constriction to both agonists, particularly in small arteries (inner diameter >120 μm). Shear stresses in small arteries were elevated during constriction and further elevated during constriction after l-NMMA. These observations suggest that NO production limits vasoconstriction in the coronary microcirculation and that the principal stimulus for this governance is elevated shear stress. The degree of shear stress moderation of constriction is heterogeneously distributed, with small arteries displaying a higher degree of shear stress regulation than arterioles. These results provide the strongest evidence to date that shear stress-mediated production of NO exerts a “braking” influence on constriction in the coronary microcirculation.

scholarly journals A theoretical model of nitric oxide transport in arterioles: frequency- vs. amplitude-dependent control of cGMP formation

2004 ◽  
Vol 286 (3) ◽  
pp. H1043-H1056 ◽  
Author(s):  
Nikolaos M. Tsoukias ◽  
Mahendra Kavdia ◽  
Aleksander S. Popel
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Soluble Guanylate Cyclase ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Cgmp Formation

Nitric oxide (NO) plays many important physiological roles, including the regulation of vascular smooth muscle tone. In response to hemodynamic or agonist stimuli, endothelial cells produce NO, which can diffuse to smooth muscle where it activates soluble guanylate cyclase (sGC), leading to cGMP formation and smooth muscle relaxation. The close proximity of red blood cells suggests, however, that a significant amount of NO released will be scavenged by blood, and thus the issue of bioavailability of endothelium-derived NO to smooth muscle has been investigated experimentally and theoretically. We formulated a mathematical model for NO transport in an arteriole to test the hypothesis that transient, burst-like NO production can facilitate efficient NO delivery to smooth muscle and reduce NO scavenging by blood. The model simulations predict that 1) the endothelium can maintain a physiologically significant amount of NO in smooth muscle despite the presence of NO scavengers such as hemoglobin and myoglobin; 2) under certain conditions, transient NO release presents a more efficient way for activating sGC and it can increase cGMP formation severalfold; and 3) frequency-rather than amplitude-dependent control of cGMP formation is possible. This suggests that it is the frequency of NO bursts and perhaps the frequency of Ca2+ oscillations in endothelial cells that may limit cGMP formation and regulate vascular tone. The proposed hypothesis suggests a new functional role for Ca2+ oscillations in endothelial cells. Further experimentation is needed to test whether and under what conditions in silico predictions occur in vivo.

Alterations of nitric oxide synthase expression and activity during rat lung transplantation

2000 ◽  
Vol 278 (5) ◽  
pp. L1071-L1081 ◽  
Author(s):  
Mingyao Liu ◽  
Lorraine Tremblay ◽  
Stephen D. Cassivi ◽  
Xiao-Hui Bai ◽  
Eric Mourgeon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Transplantation ◽  
Ex Vivo ◽  
Total Activity ◽  
No Production ◽  
Ex Vivo Model ◽  
Gene And Protein Expression ◽  
Lung Transplants ◽  
Inducible Nos

Decreased nitric oxide (NO) production has been reported during lung transplantation in patients. To study the effects of ischemia and reperfusion on endogenous NO synthase (NOS) expression, both an ex vivo and an in vivo lung injury model for transplantation were used. Donor rat lungs were flushed with cold low-potassium dextran solution and subjected to either cold (4°C for 12 h) or warm (21°C for 4 h) ischemic preservation followed by reperfusion with an ex vivo model. A significant increase in inducible NOS and a decrease in endothelial NOS mRNA was found after reperfusion. These results were confirmed in a rat single-lung transplant model after warm preservation. Interestingly, protein contents of both inducible NOS and endothelial NOS increased in the transplanted lung after 2 h of reperfusion. However, the total activity of NOS in the transplanted lungs remained at very low levels. We conclude that ischemic lung preservation and reperfusion result in altered NOS gene and protein expression with inhibited NOS activity, which may contribute to the injury of lung transplants.

scholarly journals Nitric oxide production duringVibrio choleraeinfection

1997 ◽  
Vol 273 (5) ◽  
pp. G1160-G1167 ◽  
Author(s):  
Edward N. Janoff ◽  
Hiroshi Hayakawa ◽  
David N. Taylor ◽  
Claudine E. Fasching ◽  
Julie R. Kenner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Epithelial Cells ◽  
Regional Blood Flow ◽  
Fluid Secretion ◽  
The United States ◽  
No Production ◽  
Loop Model ◽  
Ileal Loop

Vibrio cholerae induces massive intestinal fluid secretion that continues for the life of the stimulated epithelial cells. Enhanced regional blood flow and peristalsis are required to adapt to this obligatory intestinal secretory challenge. Nitric oxide (NO) is a multifunctional molecule that modulates blood flow and peristalsis and possesses both cytotoxic and antibacterial activity. We demonstrate that, compared with those in asymptomatic control subjects, levels of stable NO metabolites ([Formula: see text]/[Formula: see text]) are significantly increased in sera from acutely ill Peruvian patients with natural cholera infection as well as from symptomatic volunteers from the United States infected experimentally with V. cholerae. In a rabbit ileal loop model in vivo, cholera toxin (CT) elicited fluid secretion and dose-dependent increases in levels of[Formula: see text]/[Formula: see text]in the fluid ( P < 0.01). In contrast, lipopolysaccharide (LPS) elicited no such effects when applied to the intact mucosa. NO synthase (NOS) catalytic activity also increased in toxin-exposed tissues ( P< 0.05), predominantly in epithelial cells. The CT-induced NOS activity was Ca2+dependent and was not suppressed by dexamethasone. In conclusion, symptomatic V. cholerae infection induces NO production in humans. In the related animal model, CT, but not LPS, stimulated significant production of NO in association with increases in local Ca2+-dependent NOS activity in the tissues.

scholarly journals Constitutive nitric oxide production by rat alveolar macrophages

1998 ◽  
Vol 274 (3) ◽  
pp. L360-L368 ◽  
Author(s):  
P. R. Miles ◽  
L. Bowman ◽  
A. Rengasamy ◽  
L. Huffman
Keyword(s):  
Nitric Oxide ◽  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Lung Surfactant ◽  
Calcium Ionophore ◽  
Cell Types ◽  
Alveolar Type ◽  
No Production ◽  
No Formation

Results from previous studies suggest that alveolar macrophages must be exposed to inflammatory stimuli to produce nitric oxide (⋅ NO). In this study, we report that naive unstimulated rat alveolar macrophages do produce ⋅ NO and attempt to characterize this process. Western blot analysis demonstrates that the enzyme responsible is an endothelial nitric oxide synthase (eNOS). No brain or inducible NOS can be detected. The rate of ⋅ NO production is ∼0.07 nmol ⋅ 106cells−1 ⋅ h−1, an amount that is less than that produced by the eNOS found in alveolar type II or endothelial cells. Alveolar macrophage ⋅ NO formation is increased in the presence of extracellularl-arginine, incubation medium containing magnesium and no calcium, a calcium ionophore (A-23187), or methacholine. ⋅ NO production is inhibited by N G-nitro-l-arginine methyl ester (l-NAME) but not by N G-nitro-l-arginine,l- N 5-(1-iminomethyl)ornithine hydrochloride, or aminoguanidine. Incubation with ATP, ADP, or histamine also inhibits ⋅ NO formation. Some of these properties are similar to and some are different from properties of eNOS in other cell types. Cellular ⋅ NO levels do not appear to be related to ATP or lactate content. Alveolar macrophage production of ⋅ NO can be increased approximately threefold in the presence of lung surfactant or its major component, dipalmitoyl phosphatidylcholine (DPPC). The DPPC-induced increase in ⋅ NO formation is time and concentration dependent, can be completely inhibited by l-NAME, and does not appear to be related to the degradation of DPPC by alveolar macrophages. These results demonstrate that unstimulated alveolar macrophages produce ⋅ NO via an eNOS and that lung surfactant increases ⋅ NO formation. This latter effect may be important in maintaining an anti-inflammatory state in vivo.

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