A Novel Oral Glutarimide Derivative XC8 Suppresses Sephadex-Induced Lung Inflammation in Rats and Ovalbumin-induced Acute and Chronic Asthma in Guinea Pigs

2019 ◽  
Vol 20 (2) ◽  
pp. 146-156 ◽  
Author(s):  
Boris Ferko ◽  
Julia Romanova ◽  
Anastasia V. Rydlovskaya ◽  
Tatyana A. Kromova ◽  
Oxana V. Proskurina ◽  
...  
Keyword(s):  
Mast Cells ◽  
Lung Tissue ◽  
Guinea Pigs ◽  
Lung Inflammation ◽  
Airway Resistance ◽  
Acute Asthma ◽  
Inflammatory Cells ◽  
Goblet Cells ◽  
Chronic Asthma ◽  
Specific Airway Resistance

Background: Corticosteroids are the preferred option to treat asthma, however, they possess serious side effects and are inefficient in 10% of patients. Thus, new therapeutic approaches for asthma treatment are required. Objective: To study the efficacy of a novel glutarimide derivative XC8 in a Sephadex-induced lung inflammation in rats as well as in acute and chronic ovalbumin-induced allergic asthma in guinea pigs. Method: Rats were treated with 0.18-18 mg/kg of XC8 intragastrically 4 times (24 h and 1 h prior to and 24 h and 45 h after endotracheal administration of Sephadex). The number of inflammatory cells in bronchoalveaolar lavages (BAL) was determined. Guinea pigs were treated with 0.045 -1.4 mg/kg (acute asthma) or with 1.4 and 7.0 mg/kg of XC8 (chronic asthma) intragastrically following the sensitization with ovalbumin and during aerosol challenge. Lung inflammation, numbers of eosinophils (BAL and lung tissue), goblet cells, degranulating mast cells and specific airway resistance (sRAW) were determined. The comparator steroid drug budesonide (0.5 mg/kg for rats and 0.16 mg/kg for guinea pigs) was administered by inhalation. Results: XC8 reduced influx of eosinophils into BAL in Sephadex-induced lung inflammation model in rats (by 2.6-6.4 times). Treatment of acute asthma in guinea pigs significantly reduced eosinophils in guinea pigs in BAL (from 55% to 30%-39% of the total cell count) and goblet cells in lung tissue. In a model of acute and chronic asthma, XC8 reduced significantly the number of eosinophils and degranulating mast cells in the lung tissue. Treatment with XC8 but not with budesonide decreased the specific airway resistance in acute and chronic asthma model up to the level of naive animals. Conclusion: XC8 induced a profound anti-inflammatory effect by reducing eosinophils in BAL and eosinophils and degranulating mast cell numbers in the airway tissue. The anti-asthmatic effect of XC8 is comparable to that of budesonide. Moreover, in contrast to budesonide, XC8 was capable to reduce goblet cells and airway resistance.

Capsaicin challenge, reflex bronchoconstriction, and local action of substance P

1988 ◽  
Vol 254 (5) ◽  
pp. R845-R852 ◽  
Author(s):  
D. R. Bergren
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Airway Resistance ◽  
Intraperitoneal Administration ◽  
Whole Body ◽  
Specific Airway Resistance ◽  
Insufflation Pressure ◽  
Substance P Receptor ◽  
Bilateral Vagotomy ◽  
Substance P Release

Capsaicin was administered as an aerosol to unanesthetized guinea pigs in a whole body plethysmograph and intravenously to anesthetized guinea pigs to investigate its mechanism of action. Capsaicin increased specific airway resistance in the unanesthetized guinea pigs and increased insufflation pressure in anesthetized guinea pigs. To investigate the possible reflex action of capsaicin, an atropine or lidocaine aerosol was administered before the capsaicin aerosol challenge in unanesthetized guinea pigs. Both lidocaine and atropine reduced the effect of capsaicin. However, neither intravenous atropine nor bilateral vagotomy antagonized the effect of injected capsaicin in the anesthetized guinea pigs. To investigate further the possible action of capsaicin, spantide (a substance P receptor antagonist) was administered before capsaicin challenge. Spantide injection in anesthetized guinea pigs attenuated the effects of the intravenous capsaicin challenge. In unanesthetized guinea pigs spantide pretreatment, as an aerosol, did not ameliorate the effects of a capsaicin aerosol challenge. However, intraperitoneal administration of spantide did reduce the effect of the capsaicin aerosol challenge as the specific airway resistance increased. Therefore, capsaicin produced its effects independent of vagal reflexes, although reflex actions of capsaicin could have occurred through other pathways. Reflex actions of capsaicin, however, were demonstrable only in the unanesthetized guinea pig. Because spantide attenuated the effect of capsaicin, increased insufflation pressure and specific airway resistance due to capsaicin challenge in both unanesthetized and anesthetized guinea pigs may be attributed, at least in part, to capsaicin's induction of substance P release or the release of other tachykinins.

scholarly journals Antitussive Effect of a Pectic Arabinogalactans Isolated from Adhatoda Vasica in Vivo Experimental Conditions

2012 ◽  
Vol 12 (Supplement-1) ◽  
pp. 31-37
Author(s):  
D. Fleskova ◽  
G. Nosalova ◽  
Sudipta Saha ◽  
Shruti Bandyopadhyay ◽  
Ray Bimalendu ◽  
...  
Keyword(s):  
Citric Acid ◽  
Guinea Pigs ◽  
Airway Resistance ◽  
Negative Control ◽  
Peroral Administration ◽  
Experimental Conditions ◽  
Adhatoda Vasica ◽  
Specific Airway Resistance ◽  
Antitussive Effect

Antitussive Effect of a Pectic Arabinogalactans Isolated from Adhatoda Vasica in Vivo Experimental Conditions The herbal polysaccharides have been the subject of many studies for a very long time, especially because of their physical properties, chemical and physical modification and application. Adhatoda vasica has also been traditionally included in preparations for the relief of cough, asthma and bronchitis recommended by Ayurvedic physicians for the management of various types of respiratory disorders. In this study, we have focused on activities of pectic arabinogalactans isolated from Adhatoda vasica on experimentally induced cough reflex and the changes of specific airway resistance in vivo conditions. The substance from leaves of Adhatoda vasica was marked as P-601 and the substance from stem bark of this shrub as P-602. The aim of presented study was to compare the antitussive activity of isolated arabinogalactans with cough suppressive activity of codeine ("positive" control) and effect acquired after application of water for injection ("negative" control). Conscious male Trik guinea pigs (200-350g) were exposed to citric acid aerosol. Peroral administration of these substances in a dose of 50 mg.kg-1 body weight decreased the number of citric acid induced cough efforts in guinea pigs more effectively than codeine. They did not induce any significant changes in the values of specific airway resistance and did not provoke any observable adverse effects. Our test results confirmed that polysaccharides isolated from Adhatoda vasica in vivo conditions have expressive antitussive effect compared with the oldest and the most effective cough suppressive agent - the codeine. The positive thing is the studied substances, despite strong supressive activity, did not induced any adverse side effects.

Effect of smoking cessation on chronic waterpipe smoke inhalation-induced airway hyperresponsiveness, inflammation, and oxidative stress

2021 ◽  
Vol 320 (5) ◽  
pp. L791-L802
Author(s):  
Abderrahim Nemmar ◽  
Suhail Al-Salam ◽  
Sumaya Beegam ◽  
Nur E. Zaaba ◽  
Badreldin H. Ali
Keyword(s):  
Oxidative Stress ◽  
Smoking Cessation ◽  
Lung Tissue ◽  
Airway Resistance ◽  
Inflammatory Cells ◽  
Smoke Inhalation ◽  
Air Exposure ◽  
Lung Physiology ◽  
The Impact ◽  
And Oxidative Stress

Waterpipe smoking (WPS) prevalence is increasing globally. Clinical and laboratory investigations reported that WPS triggers impairment of pulmonary function, inflammation, and oxidative stress. However, little is known if smoking cessation (SC) would reverse the adverse pulmonary effects induced by WPS. Therefore, we evaluated the impact of WPS inhalation for 3 mo followed by 3 mo of SC (air exposure) compared with those exposed for either 3 or 6 mo to WPS or air (control) in C57BL/6 mice. To this end, various physiological, biochemical, and histological endpoints were evaluated in the lung tissue. Exposure to WPS caused focal areas of dilated alveolar spaces and foci of widening of interalveolar spaces with peribronchiolar moderate mixed inflammatory cells consisting of lymphocytes, macrophages, and neutrophil polymorphs. The latter effects were mitigated by SC. Likewise, SC reversed the increase of airway resistance and reduced the increase in the levels of myeloperoxidase, matrix metalloproteinase 9, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in lung tissue induced by WPS. In addition, SC attenuated the increase of oxidative stress markers including 8-isoprostane, glutathione, and catalase induced by WPS. Similarly, DNA damage, apoptosis, and the expression of NF-κB in the lung induced by WPS inhalation were alleviated by CS. In conclusion, our data demonstrated, for the first time, to our knowledge, that SC-mitigated WPS inhalation induced an increase in airway resistance, inflammation, oxidative stress, DNA injury, and apoptosis, illustrating the benefits of SC on lung physiology.

scholarly journals Antitussive Activity of Extracts from Fallopia Sachalinensis

2012 ◽  
Vol 12 (Supplement-1) ◽  
pp. 24-30
Author(s):  
L. Jurecek ◽  
G. Nosalova ◽  
Z. Hromadkova ◽  
Z. Kostalova
Keyword(s):  
Guinea Pigs ◽  
Airway Resistance ◽  
Folk Medicine ◽  
Scientific Basis ◽  
Positive Control ◽  
Negative Control ◽  
Peroral Administration ◽  
Cough Reflex ◽  
Specific Airway Resistance ◽  
Antitussive Activity

Antitussive Activity of Extracts from Fallopia SachalinensisGiant knotweed (Fallopia sachalinensis) and related plants are commonly used in Chinese and Japanese folk medicine. Bioactive natural products derived from them are believed to possess a variety of biologic activities. We have analyzed two polysaccharide fractions from leaves of Fallopia sachalinensis. We have focused on its activities to experimentally induced cough reflex and the changes of specific airway resistance. We have compared the observed antitussive activity with cough suppressing activity of codeine ("positive" control) and effect acquired after application of water for injection ("negative" control) using conscious male guinea pigs individually placed in a double chambers bodyplethysmograph box. Peroral administration of both polysaccharides significantly inhibited the number of coughs induced by citric acid in guinea pigs and have not significantly changed the values of specific airway resistance. Moreover, the substances in experimental animals have not provoked any notable adverse events. The biological activity observed in derivatives of Fallopia sachalinensis provides a scientific basis for the use of the plant in traditional medicines.

scholarly journals Effects of Pelargonium sidoides and Coptis Rhizoma 2 : 1 Mixed Formula (PS + CR) on Ovalbumin-Induced Asthma in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Byung Gu Min ◽  
Sang Mi Park ◽  
Youn Woong Choi ◽  
Sae Kwang Ku ◽  
Il Je Cho ◽  
...  
Keyword(s):  
Mast Cells ◽  
Lung Tissue ◽  
Inflammatory Cells ◽  
Tissue Homogenate ◽  
Pelargonium Sidoides ◽  
Cell Counts ◽  
Septal Thickness ◽  
Differential Cell ◽  
Lung Tissue Homogenate ◽  
Dose Dependent

Pelargonium sidoides (PS) is traditionally used to treat respiratory and gastrointestinal infections, dysmenorrhea, and hepatic disorders in South Africa. Coptis Rhizoma (CR) is used to treat gastroenteric disorders, cardiovascular diseases, and cancer in East Asia. In the present study, we intended to observe the possible beneficial antiasthma effects of PS and CR on the ovalbumin- (OVA-) induced asthma C57BL/6J mice. Asthma in mice was induced by OVA sensitization and subsequent boosting. PS + CR (300 and 1,000 mg/kg; PO) or dexamethasone (IP) was administered once a day for 16 days. The changes in the body weight and gains, lung weights and gross inspections, total and differential cell counts of leukocytes in bronchoalveolar lavage fluid (BALF), serum OVA-specific immunoglobulin E (OVA-sIgE) levels, interleukin-4 (IL-4) and IL-5 levels in BALF and lung tissue homogenate, and IL-4 and IL-5 mRNA levels in lung tissue homogenates were analyzed with lung histopathology: mean alveolar surface area (ASA), alveolar septal thickness, numbers of inflammatory cells, mast cells, and eosinophils infiltrated in the alveolar regions, respectively. Significant increases in lung weights, total and differential cell counts of leukocytes in BALF, serum OVA-sIgE levels, and IL-4 and IL-5 levels in BALF and lung tissue homogenate were observed in OVA control as compared to those of intact control. In addition, OVA control showed a significant decrease in mean ASA and increases in alveolar septal thickness, numbers of inflammatory cells, mast cells, and eosinophils infiltrated in alveolar regions. However, these allergic and inflammatory asthmatic changes were significantly inhibited by PS + CR in a dose-dependent manner. In this study, PS + CR showed dose-dependent beneficial effects on OVA-induced asthma in mice through anti-inflammatory and antiallergic activities. Therefore, it is expected that PS + CR have enough potential as a new therapeutic agent or as an ingredient of a medicinal agent for various allergic and inflammatory respiratory diseases including asthma.

scholarly journals Ganoderic Acid A Alleviates OVA-Induced Asthma in Mice

Inflammation ◽  
2021 ◽  
Author(s):  
Xinhua Lu ◽  
Chenyang Xu ◽  
Rui Yang ◽  
Guojun Zhang
Keyword(s):  
Lung Tissue ◽  
Lung Inflammation ◽  
Inflammatory Cell ◽  
Inflammatory Cells ◽  
Interleukin 4 ◽  
Model Group ◽  
Ganoderic Acid ◽  
Tissue Sections ◽  
Asthma Model

AbstractThe aim of this study is to investigate the effects of ganoderic acid A (GAA) on OVA-induced asthma in mice. Mouse asthma model was established by ovalbumin (OVA) in vitro. Diff-Quik staining was used to observe the total numbers of cells and the number of classification cells in each group, and HE staining was used to observe lung inflammation in lung tissue sections. ELISA was used to detect the effect of GAA on the levels of interleukin-4 (IL-4), IL-5, and IL-13 in serum and lung tissue. The expression levels of TLR/NF-κB were detected by Western blot. Immunohistochemistry was used to observe the expression changes of TLR4 and P-P65. Compared with the normal group, the inflammatory cell count, IL-4, IL-5, and IL-13 expression in the model group increased, and TLR/NF-kB signal protein expression increased. Compared with the model group, in GAA group, the number of inflammatory cells, the expression of IL-4, IL-5, and IL-13 decreased, and the expression of TLR/NF-kB signaling protein decreased. GAA regulated lung inflammation in asthmatic mice by inhibiting TLR/NF-kB signaling pathway.

Acute transient SO2-induced airway hyperreactivity: effects of nedocromil sodium

1988 ◽  
Vol 65 (3) ◽  
pp. 1119-1124 ◽  
Author(s):  
D. M. Jackson ◽  
R. P. Eady
Keyword(s):  
Mast Cells ◽  
Epithelial Cells ◽  
Lung Inflammation ◽  
Goblet Cells ◽  
Airway Hyperreactivity ◽  
Nedocromil Sodium ◽  
Bronchial Responsiveness ◽  
Inflammatory Agent ◽  
Before And After ◽  
Number Of Cells

The effect of nedocromil sodium given as an aerosol on the immediate lung hyperreactivity and lung inflammation caused by a 2-h exposure to 400 ppm SO2 has been studied in dogs. Exposure to SO2 caused an immediate increase in bronchial responsiveness to histamine aerosol that lasted for approximately 2 h. The total number of cells recovered by bronchial lavage increased postexposure. Initially this increase was caused by epithelial cells (0.25 and 1 h) and later by neutrophils (1, 2, 3, and 4 h). There was no significant change in the numbers of lymphocytes, macrophages, eosinophils, goblet cells, or mast cells in the lavages. Nedocromil sodium (approximately 8 mg) given as a nebulized aerosol before and after SO2 exposure prevented the increase in lung reactivity and attenuated the increase in the total number of cells (epithelial cells and neutrophils) in the lung lavages for the 4 h after exposure. Nedocromil sodium did not affect the reactivity of normal dogs to histamine aerosol. Nedocromil sodium appears to act as an anti-inflammatory agent in this model of lung inflammation, preventing an increase in lung reactivity and reducing cell infiltration. The mechanism of action of nedocromil sodium in this model is unknown.

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