Reduction In Nitric Oxide Concentration Research Articles

Dapsone Protects Against Lithium-Pilocarpine-Induced Status Epilepticus in Rats through Targeting Tumor Necrosis Factor-α and Nitrergic Pathway.

Status epilepticus (SE) results in permanent neuronal brain damage in the central nervous system. One of the complex etiologies underlying SE pathogenesis is neuroinflammation. Dapsone has been recently considered as a potential neuroprotective agent in neuroinflammatory conditions. Therefore, the present study aims to investigate effects of dapsone on lithium-pilocarpine-induced SE in rats and assess whether tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO) pathway participate in this effect. SE was established by injecting lithium chloride (127 mg/kg, intraperitoneally [i.p.]) and pilocarpine (60 mg/kg, i.p.). The animals received pre-treatment dapsone (2, 5, 10, and 20 mg/kg, oral gavage) and post-treatment dapsone (10 mg/kg). Subsequently, seizure score and mortality rate were documented. To assess the underlying signaling pathway, L-Nω-Nitro-L-arginine methyl ester hydrochloride (a non-specific NO synthase [NOS] inhibitor), 7-nitroindazole (a specific neuronal NOS inhibitor), and aminoguanidine (a specific inducible NOS inhibitor) were administered 15 minutes before dapsone (10 mg/kg) pre- or post-treatment. Hippocampal tissue TNF-α and NO concentrations were quantified using the enzyme-linked immunosorbent assay method. Dapsone (10 mg/kg) pre-and post-treatment significantly attenuated the increased seizure score and mortality rate due to lithium-pilocarpine-induced SE. The development of SE in animals was associated with higher TNF-α and NO metabolites levels, which notably decreased in the dapsone-treated rats. Moreover, co-administration of NOS inhibitors with dapsone markedly reversed the anti-epileptic effects of dapsone and caused an escalation in TNF-α level but a significant reduction in NO concentration level. It seems that dapsone may exert an anti-epileptic effect on lithium-pilocarpine-induced SE through TNF-α inhibition and modulation of the nitrergic pathway.

Ameliorative effects of Moringa oleifera (MO) seeds on L‐NAME‐induced hypertension in rats

Cardiovascular diseases including hypertension, have been recognized as leading causes of death worldwide. In this study we investigated the effect of Moringa oleifera on L‐NAME induced hypertension in rats. Fifty (50) Wistar albino rats were grouped into five groups. Group A, the control, was administered water only. Groups B‐E received orally, 40 mg/kg of L‐NAME only, 40 mg/kg of L‐NAME and 10% MO feed inclusion, 40 mg/kg of L‐NAME and 20% MO feed inclusion, and 40 mg/kg of L‐NAME and 10 mg/kg of lisinopril, respectively for 35 days. Treatment with L‐NAME caused a significant (p< 0.05) reduction in Nitric oxide concentration as well as an increase in blood pressure measurements when compared with the control. These were however ameliorated by the administration of MO seeds and lisinopril. Markers of oxidative stress (malondialdehyde and Hydrogen peroxide) increased significantly (p<0.05) in the group treated with L‐NAME alone while the administration of MO seeds and lisinopril caused a significant decrease in their values when compared with the controls. Also, the administration of L‐NAME caused a significant (p<0.05) decrease in the activities of enzymic antioxidants (Glutathione peroxidase and Glutathione‐S‐transferase) while there was reduction in the levels of reduced glutathione level as well as activities of superoxide dismutase, glutathione peroxidase and glutathione‐S‐transferase when compared with the control. These were however significantly (p<0.05) ameliorated by the administration of MO seeds and lisinopril. Taken together, Moringa oleifera seed inclusion in the feed of rats ameliorated L‐NAME induced hypertension by improving Nitric oxide bioavailability as well as its antioxidant activitiesSupport or Funding InformationNone

Neuroprotective effects of isoflurane against lipopolysaccharide-induced neuroinflammation in BV2 microglial cells by regulating HMGB1/TLRs pathway.

Microglia, as the first line of defence of the central nervous system (CNS), has a major role in inflammatory response. It was reported that isoflurane has a neuroprotective role in the pathological process of CNS by interfering with inflammatory response. While the mechanism and function of isoflurane in microglia-mediated inflammation are still not clearly articulated. In our study, the inflammation model was established by the activation of lipopolysaccharide (LPS) in BV2 cells in vitro. The results demonstrated that isoflurane inhibited the release of nitric oxide (NO) and enhanced the survival of BV2 cells, meanwhile, isoflurane reduced the levels of inflammatory factors and downregulated the expressions of inflammation-related genes and proteins in LPS-mediated BV2 cells. Furthermore, we demonstrated that overexpression of high-mobility group box 1 protein (HMGB1) could reverse the reduction in NO concentration, enhancement of cell BV2 viability and inhibition of inflammatory response, which were mediated by isoflurane in LPS-induced BV2 cells. Therefore, we suggested that isoflurane inhibits the activation of LPS-induced neuro microglia and reduces the release of inflammatory factors by regulating HMGB1, suggesting that isoflurane might play a protective role in LPS-induced neuroinflammation through the HMGB1 pathway.

Nitric oxide improves tolerance to arsenic stress in Isatis cappadocica desv. Shoots by enhancing antioxidant defenses

Arsenic (As) is a toxic metalloid that severely hampers plant growth and also poses health risks for humans through the food chain. Although nitric oxide (NO) is known to improve plant resistance to multiple stresses including metal toxicity, little is known about its role in the As tolerance of hyperaccumulator plants. This study investigates the role of the exogenously applied NO donor, sodium nitroprusside (SNP), in improving the As tolerance of Isatis cappadocica, which has been reported to hyperaccumulate As. Exposure to toxic As concentrations significantly increases NO production and damages the cell membrane, as indicated by increased hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations, thereby reducing plant growth. However, the addition of SNP improves growth and alleviates As-induced oxidative stress by enhancing the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione S-transferase (GST), glutathione (GSH), as well as proline and thiol concentrations, thereby confirming the beneficial role played by NO in increasing As stress tolerance. Furthermore, the As-induced decrease in growth and the increase in oxidative stress were more marked in the presence of bovine hemoglobin (Hb; a NO scavenger) and N(G)-nitro-l-arginine methyl ester (l-NAME; a NO synthase inhibitor), thus demonstrating the protective role of NO against As toxicity. The reduction in NO concentrations by l-NAME suggests that NOS-like activity is involved in the generation of NO in response to As in I. cappadocica.

Polysaccharide from Spirulina platensis ameliorates diphenoxylate-induced constipation symptoms in mice

The aim of this study is to probe new functions of a polysaccharide from Spirulina platensis (PSP) on constipation and intestinal microbiota in mice. Diphenoxylate-induced constipation in mice was treated with different doses of PSP, followed by examining the defecation patterns, levels of acetyl cholinesterase (AchE), nitric oxide (NO), and tissue section histopathology. The composition of intestinal microbiota was determined by genome sequencing analysis of the 16S rDNA. This study found that the average molecular weight of PSP was 29, 600 Da, and mainly monosaccharides of PSP were rhamnose (24.7%), glucose (16.15%) and galactose (13.32%). The beneficial effects of PSP treatment include defecation improvement, increase of AchE activity, reduction of NO concentration, renovation of the damaged intestinal villus and affection on the expression of some related genes in the constipated mice. In addition, PSP had significant effects on the gut microbiota, showing the enhancement in abundance of beneficial bacteria including Akkermansia, Lactobacillus, Butyricimonas, Candidatus Arthromitus and Prevotella, and the reduction in abundance of harmful bacteria such as Clostridium and Dorea. The present s uncovered a new function of PSP, indicating that PSP could be used in constipation therapies.

The tamoxifen derivative ridaifen-B is a high affinity selective CB2 receptor inverse agonist exhibiting anti-inflammatory and anti-osteoclastogenic effects

Selective estrogen receptor modulators (SERMs) target estrogen receptors (ERs) to treat breast cancer and osteoporosis. Several SERMs exhibit anti-cancer activity not related to ERs. To discover novel anti-cancer drugs acting via ER-independent mechanisms, derivatives of the SERM tamoxifen, known as the “ridaifen” compounds, have been developed that exhibit reduced or no ER affinity, while maintaining cytotoxicity. Tamoxifen and other SERMs bind to cannabinoid receptors with moderate affinity. Therefore, ER-independent effects of SERMs might be mediated via cannabinoid receptors. This study determined whether RID-B, a first generation ridaifen compound, exhibits affinity and/or activity at CB1 and/or CB2 cannabinoid receptors. RID-B binds with high affinity (Ki = 43.7 nM) and 17-fold selectivity to CB2 over CB1 receptors. RID-B acts as an inverse agonist at CB2 receptors, modulating G-protein and adenylyl cyclase activity with potency values predicted by CB2 affinity. Characteristic of an antagonist, RID-B co-incubation produces a parallel-rightward shift in the concentration-effect curve of CB2 agonist WIN-55,212-2 to inhibit adenylyl cyclase activity. CB2 inverse agonists are reported to exhibit anti-inflammatory and anti-ostoeclastogenic effects. In LPS-activated macrophages, RID-B exhibits anti-inflammatory effects by reducing levels of nitric oxide (NO), IL-6 and IL-1α, but not TNFα. Only reduction of NO concentration by RID-B is mediated by cannabinoid receptors. RID-B also exhibits pronounced anti-osteoclastogenic effects, reducing the number of osteoclasts differentiating from primary bone marrow macrophages in a cannabinoid receptor-dependent manner. In summary, the tamoxifen derivative RID-B, developed with reduced affinity for ERs, is a high affinity selective CB2 inverse agonist with anti-inflammatory and anti-osteoclastogenic properties.

Nitric Oxide Concentration and Other Salivary Changes after Insertion of New Complete Dentures in Edentulous Subjects.

Objective. To assess changes in levels of salivary nitric oxide (NO) after insertion of new complete dentures and its association with clinical and salivary parameters. Methods. Nineteen fully edentulous subjects were included, mean age 64.4. Unstimulated whole saliva was collected before and after insertion of the dentures, at follow-up visits, and after 12 months. The concentration of the final stable NO product (nitrite) was measured by a colorimetric assay based on the Griess reaction. Clinical parameters were assessed during all clinical visits. Results. Functional adaptation to the dentures progressively improved, with no complaints at the long-term follow-up. NO concentration was not influenced by the level of functional adaptation, presence of injuries to the mucosa, salivary flow, and saliva viscosity. Pairwise comparison showed a reduction in NO concentration at the first follow-up compared to baseline values but differences were not statistically significant. Significant differences were observed in NO concentrations at the long-term follow-up when compared to the first (p = 0.024) and second (p = 0.027) visits. Conclusion. NO concentration reduced after denture insertion and returned to baseline levels in the long-term follow-up. This appears to be an autonomic response of the body and provides valuable complementary information for the management of the edentulous patient.

Interleukin-1 receptor antagonist decreases cerebrospinal fluid nitric oxide levels and increases vasopressin secretion in the late phase of sepsis in rats.

The aim of this study was to analyze the effect of IL-1ra (an Interleukin-1 receptor antagonist) on sepsis-induced alterations in vasopressin (AVP) and nitric oxide (NO) levels. In addition, IL-1ra effect on the hypothalamic nitric oxide synthase (NOS) activities and survival rate was also analyzed. After Wistar rats were intracerebroventricular injected with IL-1ra (9 pmol) or vehicle (PBS 0.01 M), sepsis was induced by cecal-ligation and puncture (CLP). Blood, CSF, and hypothalamic samples were collected from different groups of rats (n = 8/group) after 4, 6, and 24 h. AVP and NO levels were greatly increased in CLP. Both total NOS and inducible NOS (iNOS) activities were also greatly increased in CLP rats. These changes in AVP, NO, and NOS were not observed in sham-operated control rats. IL-1ra administration did not alter plasma AVP levels after 4 and 6 h as compared to vehicle in CLP animals but after 24 h were significantly (P < 0.01) higher in IL-1ra-treated animals. IL-1ra administration significantly (P < 0.01) decreased NO concentration in CSF but not in plasma. Both total NOS and iNOS activities were also significantly decreased by IL-1ra at 24 h in CLP animals. Moreover, the 24 h survival rate of IL-1ra-treated rats increased by 38 % in comparison to vehicle administered animals. The central administration of IL-1ra increased AVP secretion in the late phase of sepsis which was beneficial for survival. We believe that one of the mechanisms for this effect of IL-1ra is through reduction of NO concentration in CSF and hence lower hypothalamic iNOS activities in the septic rats.

The quantitative effect of an accessory ostium on ventilation of the maxillary sinus

The airflow and gas exchange behaviors of the human maxillary sinus were quantified to better understand the effect of an accessory ostium (AO). An anatomically correct numerical domain was constructed using CT data from a male patient with mild nasal obstruction. For the purpose of comparison, a numerical model without an AO was also generated by artificially removing the AO from the original model using CAD software. A steady-flow field through the nasal cavity was simulated using ANSYS-FLUENT v13.0 with a target flow rate of 250 ml/s. The Volume of Fluid (VOF) method was used to investigate the concentration field of nitric oxide (NO) initially filled in the maxillary sinus. The simulation results showed that a transit flow through the maxillary sinus developed in the presence of an AO. As the flow entered the sinus through either a natural or accessory ostium from the middle meatus, the velocity was significantly reduced to a local maximum of approximately 0.034 m/s inside the sinus. This by-pass flow rate through the sinus of 2.186×10(-1) to 3.591×10(-1) ml/s was a small fraction of the total flow rate inhaled from the nostril, but it effectively changed the local flow topology and led to a larger reduction in NO concentration in the maxillary sinus. This more rapid reduction in NO concentration was due to enhanced ventilation activity afforded by convective transport of the transit stream through the flow path connecting the natural ostium and the AO. The inspiration and expiration phases were qualitatively similar in flow pattern except for the flow direction in the maxillary sinus, suggesting that the AO plays a similar physiological role during both inspiration and expiration in terms of ventilation.

Molecular adsorbent recirculating system is ineffective in the management of type 1 hepatorenal syndrome in patients with cirrhosis with ascites who have failed vasoconstrictor treatment

BackgroundThe pathogenetic mechanism of hepatorenal syndrome (HRS) is paradoxical renal vasoconstriction consequent upon systemic and splanchnic arterial vasodilatation. Molecular adsorbent recirculating system (MARS) is a specialised form of dialysis that...

Exhaled nitric oxide in single and repetitive prolonged exercise

This study was performed to determine the influence of single and repetitive exercise on nitric oxide (NO) concentration in the lung. Exhaled NO concentration (FENO) was measured during a constant-flow exhalation manoeuvre (170 ml · s−1, against a 10 cmH2O resistance) in healthy individuals (a) during and after a 100-min square-wave exercise of between 25 and 60% of maximal power output (n = 18) and (b) before and after five successive prolonged exercises (90 – 120 min, 75 – 85% of maximal heart rate) separated by 48 or 24 h (n = 8). The FENO0.170 was decreased during and after the 100-min exercise test (mean± s [xbar] : 58.5 ± 3.7% and 76.7 ± 5.2% of resting value at 90 min of exercise and 15 min post-exercise, respectively; P < 0.05). The five successive exercise sessions induced a similar post-exercise FENO0.170 decrement (73.1 ± 2.9% of resting value 15 min post-exercise), while basal FENO0.170 values were not different between the five sessions (P > 0.05). These results suggest that prolonged exercise induces a reduction in NO concentration within the lung that lasts for several minutes after the end of exercise. However, repetitive exercises (at least every 24 h) allow complete NO recovery from one session to another. The implication of such a decrease in NO availability within the lung remains to be clarified.

Endogenous nitric oxide modulates GABAergic transmission to granule cells in adult rat cerebellum.

Nitric oxide (NO) is a gaseous neurotransmitter which plays an important role in neuronal signalling and plasticity throughout the brain. In the cerebellum, NO synthase (NOS) is expressed in parallel fibres and within the internal granule cell layer (IGL). During development there are changes in NOS concentration, distribution and activity within the IGL, suggesting NO may play a role in IGL function. Therefore, the actions of NO in the IGL were investigated. The similar actions of a range of NOS inhibitors and NO scavengers strongly suggested the presence of a tonic level of endogenous NO in the IGL. Both the neuronal and inducible forms of NOS appeared to be sources of this endogenous NO. The effects observed following a reduction in the concentration of endogenous NO were consistent with enhanced granule cell GABAA receptor activation. For example, a reduction in NO concentration led to an increase in the frequency of action potential-dependent phasic GABAergic inhibitory postsynaptic currents (IPSCs) and produced a TTX-insensitive GABAA receptor-mediated current. A direct action of NO on Golgi cell membrane potential and input resistance accounted for the increase in the frequency of phasic GABA release. The mechanism underlying the tonic GABA current is unclear but does not appear to be via the modulation of GABA uptake or the activation of nicotinic acetylcholine receptors. NO is a potentially novel mechanism for tuning GABAergic signalling to granule cells and therefore modulating the throughput of an important cerebellar circuit.

Quantitative laser-saturated fluorescence measurements of nitric oxide in a heptane-fueled lean direct-injection spray flame at varying global equivalence ratios

We report the influence of equivalence ratio on nitric oxide (NO) concentration profiles in an unconfined heptane spray flame at atmospheric pressure. The associated burner is based on the lean direct-injection design and incorporates a pressure-atomized, hollow-cone spray nozzle. Helical vanes in the air passage coupled with a divergent exit and preheated air produce a strongly swirling, clean, blue flame. NO concentration profiles are measured using laser-saturated fluorescence (LSF) at four axial heights above the burner. Because of the liquid droplet environment, an extension of LSF utilizing a Mie-scattering back-ground subtraction technique is required to make quantitative measurements of NO concentration. The NO profiles are measured in three flames with global equivalence ratios of 1.0, 0.9, and 0.8. Probe measurements of CO 2 and O 2 mole fractions are used to determine representative effective equivalence ratios, which are lower than the global equivalence ratios because of significant entrainment of ambient air Through an analysis of area-averaged NO concentrations at various axial heights, the downstream [NO] is found to be mainly redistributed as the flame spreads owing to the intense recirculation of combustion products. Moreover, comparisons of [NO] profiles as a function of equivalence ratio demonstrate that dilution air is a large influence in the reduction of NO concentration at equivalence ratios leaner than stoichiometric.