Rat Model Of Allergic Asthma Research Articles

PI3Kγδ inhibition suppresses key disease features in a rat model of asthma

BackgroundTwo isoforms of Phosphoinositide 3-kinase (PI3K), p110γ and p110δ, are predominantly expressed in leukocytes and represent attractive therapeutic targets for the treatment of allergic asthma. The study aim was to assess the impact of administration of an inhaled PI3Kγδ inhibitor (AZD8154) in a rat model of asthma.MethodsFirstly, we checked that the tool compound, AZD8154, inhibited rat PI3K γ & δ kinases using rat cell-based assays. Subsequently, a time-course study was conducted in a rat model of asthma to assess PI3K activity in the lung and how it is temporally associated with other key transcription pathways and asthma like features of the model. Finally, the impact on lung dosed AZD8154 on target engagement, pathway specificity, airway inflammation and lung function changes was assessed.ResultsData showed that AZD8154 could inhibit rat PI3K γ & δ isoforms and, in a rat model of allergic asthma the PI3K pathway was activated in the lung. Intratracheal administration of AZD8154 caused a dose related suppression PI3K pathway activation (reduction in pAkt) and unlike after budesonide treatment, STAT and NF-κB pathways were not affected by AZD8154. The suppression of the PI3K pathway led to a marked inhibition of airway inflammation and reduction in changes in lung function.ConclusionThese data show that a dual PI3Kγδ inhibitor suppress key features of disease in a rat model of asthma to a similar degree as budesonide and indicate that dual PI3Kγδ inhibition may be an effective treatment for people suffering from allergic asthma.

Revealing the mechanisms of Arisaema cum Bile on allergic asthma with systematic pharmacology approach-experimental validation

Arisaema cum Bile (Dan Nanxing in Chinese, DNX) have been employed to treat allergic asthma. However, the active components and its mechanisms remain unknown. Therefore, the systematic pharmacology approach-experimental validation was performed in this study. Each 5, 6, and 10 compounds of DNX were obtained by HPLC analysis, TCMSP, and literature report, respectively. A total of 379 targets on all these compounds were acquired from Swiss Target Prediction, and 1973 targets on allergic asthma were predicated. The KEGG enrichment analysis was performed. Furthermore, a rat model of allergic asthma was established and DNX (450 mg/kg, p.o.) was given for 2 weeks. DNX treatment prevented OVA-induced pathological changes in lung cell of irregular arrange and necrotic bronchial epithelial. It also decreased inflammatory cytokines IL-4, IL-5, and IL-13 of serum and BALF, and increased IL-12 and IFN-γ. The main MAPK signaling pathway predicted by KEGG enrichment was verified, as indicated by the decreased protein expression of JNK (p < 0.05 &p < 0.01), ERK (p < 0.05), and p38 MAPK (p < 0.01) in lung tissue. These findings indicated that DNX attenuated OVA-induced allergic asthma mainly by decreasing the MAPK signaling pathway.

Dapagliflozin mitigates ovalbumin-prompted airway inflammatory-oxidative successions and associated bronchospasm in a rat model of allergic asthma

ABSTRACT Background Asthma is a chronic inflammatory lung disease that universally affects millions of people. Despite numerous well-defined medications, asthma is poorly managed. This study aims to clarify the potential therapeutic effect of Dapagliflozin (DAPA) against lung inflammation, oxidative stress, and associated bronchospasm in OVA-sensitized rat asthma model. Research design and methods Twenty-five rats were allocated into (Control, Asthma, DEXA, DAPA, and DAPA+DEXA). All treatments were administered orally once a day for two weeks. The BALF levels of IL-17, TNFα, IL-1β, and MCP-1 were determined to assess airway inflammation. For oxidative stress determination, BALF MDA levels and TAC were measured. The BALF S100A4 level and NO/sGC/cGMP pathway were detected. Lung histopathological findings and immunohistochemical investigation of eNOS and iNOS activities were recorded. Results DAPA significantly reduced (p < 0.001) airway inflammatory-oxidative markers (IL-17, TNFα, IL-1β, MCP1, and MDA), but increased (p < 0.001) TAC, and mitigated bronchospasm by activating NO/sGC/cGMP and reducing S100A4 (p < 0.001). The biochemical and western blot studies were supported by histopathological and immunohistochemical investigations. Conclusions DAPA presents a new prospective possibility for future asthma therapy due to its anti-inflammatory, anti-oxidant, and bronchodilator properties. DAPA has the property of reducing Dexamethasone (DEXA)-associated unfavorable effects during asthma treatment.

Influence of Consumption of Two Peruvian Cocoa Populations on Mucosal and Systemic Immune Response in an Allergic Asthma Rat Model.

Different cocoa populations have demonstrated a protective role in a rat model of allergic asthma by attenuating the immunoglobulin (Ig) E synthesis and partially protecting against anaphylactic response. The aim of this study was to ascertain the effect of diets containing two native Peruvian cocoa populations (“Amazonas Peru” or APC, and “Criollo de Montaña” or CMC) and an ordinary cocoa (OC) on the bronchial compartment and the systemic and mucosal immune system in the same rat model of allergic asthma. Among other variables, cells and IgA content in the bronchoalveolar lavage fluid (BALF) and serum anti-allergen antibody response were analyzed. The three cocoa populations prevented the increase of the serum specific IgG1 (T helper 2 isotype). The three cocoa diets decreased asthma-induced granulocyte increase in the BALF, which was mainly due to the reduction in the proportion of eosinophils. Moreover, both the OC and CMC diets were able to prevent the leukocyte infiltration caused by asthma induction in both the trachea and nasal cavity and decreased the IgA in both fecal and BALF samples. Overall, these results highlight the potential of different cocoa populations in the prevention of allergic asthma.

Allergen disrupts amygdala-respiration coupling

Allergic asthma affects both the respiratory function and central nervous system. Communication between the amygdala and respiratory control system is critical for regulating breathing function. To date, no study provides the effect of allergic inflammation on amygdala-respiration coupling. Here, we simultaneously recorded respiration and local field potentials of the amygdala during awake immobility in a rat model of allergic asthma. A decreased synchrony was found between amygdala and respiration in asthmatic rats. Allergen also reduced the modulatory effect of the respiration phase on amygdala power at delta, theta and gamma2 (80−120 Hz) frequencies. Moreover, in the animal model of allergic asthma, delta and theta oscillations strongly coordinate local gamma2 activity in the amygdala. These findings suggest that allergen can induce brain alterations and therefore shed light on future works to address how disruption of amygdala-respiration coupling contributes to respiratory dysfunction in allergic asthma.

Embelin Alleviates Severe Airway Inflammation in OVA-LPS-Induced Rat Model of Allergic Asthma.

BackgroundAsthma is a chronic lung disease, which causes wheezing, tightness in the chest, shortness of breath and coughing. In the wake of coronavirus disease 2019 (COVID-19), which affect the lungs, asthma patients are at high risk. Embelin, a natural benzoquinone obtained mainly from Embelia ribes Burm, has excellent biological properties, including protection against acute asthma. However, since asthma is a chronic and multi-factorial inflammatory disease, asthma conferred by a single allergen in an animal may not be clinically significant. Therefore, the purpose of the current study was to evaluate the effectiveness of embelin against ovalbumin (OVA)-lipopolysaccharide (LPS)-induced severe airway inflammation in experimental animals and to investigate the plausible mechanism of action.MethodsRats (n=36) were divided into six groups. Group I served as a normal control. Groups II–VI were sensitised with severe allergens (OVA and LPS) on day 7, 14 and 21, followed by OVA and LPS challenge for 30 min three times/week for 3 weeks. Group II acted as an asthmatic disease control and received only vehicle. On the other hand, groups III–V received embelin (12.5, 25 and 50 mg/kg, P.O. respectively) while group VI received a standard dexamethasone (2.5 mg/kg, P.O.) for 15 days from day 27. Lung function parameters, including the respiratory rate, tidal volume and airflow rate were measured at the end of the experiment (day 42). The total and differential counts of leukocytes in the blood and bronchoalveolar fluid (BALF) were calculated. Th2-mediated serum pro-inflammatory cytokines such as interleukin (IL)-4, IL-5 and IL-13 levels were analyzed. At the end of the study protocol, the lung tissues were removed for a histopathology study. Additionally, a molecular docking simulation on embelin and standard dexamethasone was applied to support the in vivo findings.ResultsSignificant inhibition of eosinophils, neutrophils, lymphocytes and monocytes in the blood and the BALF was seen in the groups, which received embelin (25 and 50 mg/kg) and dexamethasone (2.5 mg/kg). Moreover, the lung function parameters were normalised by embelin (25 and 50 mg/kg) treatment significantly. The lung histopathological changes confirmed the protective effect of embelin against severe airway inflammation. The docking findings indicated good binding efficacy of embelin to IL-13.ConclusionOverall, our findings indicate that embelin can alleviate severe airway inflammation in OVA-LPS-induced model of allergic asthma occurring by suppression of Th2-mediated immune response. Due to its promising anti-asthmatic effect, it is recommended that embelin should be investigated in clinical trials against asthma. It should also be further explored against COVID-19 or COVID-like diseases due to its ameliorative effects on cytokines and immune cell infiltration.

Study on the Mechanism of Jiawei Shengjiang Powder in Improving Male Asthma-Induced Asthenospermia Based on Network Pharmacology and Bioinformatics.

BackgroundJiawei Shengjiang Powder (JWSJP) is a classical Chinese medicinal formula, which has been widely applied in the treatment of asthma and complications for many years due to its curative effect.AimTo verify the effect of JWSJP in improving abnormal sperm motility caused by asthma and to explore its potential mechanism.Materials and MethodsThe active compounds of JWSJP were obtained from high performance liquid chromatography tandem mass spectrometry and the Traditional Chinese Medicine System Pharmacology. The key active components and targets of JWSJP were predicted based on network pharmacological analysis and bioinformatics research. Rats were randomly divided into normal, model and treatment groups. The rat model of allergic asthma was induced by intraperitoneal injection of ovalbumin solution. The experiment judged improvement of semen quality by evaluating sperm motility, and detected the expression of related proteins in testicular tissue of Sprague-Dawley rats by RT-qPCR and Western blot methods. Hematoxylin and eosin (HE) staining was used to observe the changes in testicular tissue structure in rats.ResultsThrough the analysis of network pharmacology and bioinformatics, it was found that beta-sitosterol, quercetin, gallic acid, pelargonidin and kaempferol were the key active components of Jiawei Shengjiang Powder. Tumor necrosis factor (TNF), interleukin-6 (IL-6) and insulin (INS) genes are crucial targets of JWSJP in the treatment of spermatogenic dysfunction caused by acute asthma. After 8 weeks of intervention, compared with the model group, the treatment group had significantly improved sperm motility (P < 0.05). There were significant differences in TNF, IL6, and INS proteins in the treatment group, and the HE staining of testicular tissue structure in the treatment group was significantly improved.ConclusionJWSJP can improve the abnormal sperm motility induced by asthma, and its mechanism may be related to the expression of related proteins and mRNA of TNF, IL6, and INS.

Silencing of ADAM33 restrains proliferation and induces apoptosis of airway smooth muscle cells in ovalbumin-induced asthma model.

A defibrinogen and metalloproteinase 33 (ADAM33) was reported to play an important role in asthma. Furthermore, ADAM33 may play a possible role in airway remodeling due to its high expression in myo-/fibroblasts, epithelium, as well as the airway smooth muscle cells (ASMCs). Thus, the study is supposed to investigate the effect of the downregulation of ADAM33 on the proliferation and apoptosis of ASMCs in allergic asthma. An ovalbumin-induced asthma model in rats was established for investigating the function of the silencing of ADAM33. ASMCs were cultured and divided into four groups after transfection. The messenger RNA and protein expressions of ADAM33 were measured by reverse transcription quantitative polymerase chain reaction and Western blot analysis. Cell proliferation was tested by cell counting kit-8 and cell apoptosis by TdT-mediated dUTP nick-end labeling. The allergic asthma rats showed a large number of inflammatory cell infiltration, airway smooth muscle hypertrophy and hyperplasia, and increased WA t , WA m , and numbers of bronchial smooth muscle nucleus. Additionally, increased numbers of eosinophils and neutrophils, expressions of immunoglobulin E and interleukin-4, content of airway air pressure, and NO, although decreased in expression of interferon-γ, were exhibited in rats with allergic asthma. In our study, upregulated ADAM33 was found, and after the silencing of ADAM33, decreased proliferation and increased apoptosis of ASMCs were observed. The study evidences that silencing of ADAM33 can decrease the proliferation and increase the apoptosis of ASMCs in a rat model of allergic asthma, suggesting ADAM33 represents a potential investigative focus target aiding allergic asthma.

The roles of the TLR/NF‑κB signaling pathway in the mutual interactions between the lung and the large intestine.

The ‘exterior-interior relationship between the lung and the large intestine’ is a classical basic theory in Traditional Chinese Medicine. The present study aimed to investigate the roles of the toll like receptor/nuclear factor-κB (TLR/NF-κB) signaling pathway in the mutual interactions between the lung and the large intestine. A rat model of allergic asthma complicated with intestinal flora disorder was established by oral administration of Candida albicans and intraperitoneal injection with ovalbumin. The number of inflammatory cells and expression levels immunoglobulin (Ig)E, secretory IgA, interleukin (IL)-4 and interferon-γ in serum and bronchoalveolar lavage fluid were subsequently measured. Bacterial colonies and expression of 16S ribosomal DNA were studied in feces samples and pathological alterations of lung tissues were identified. Furthermore, the expression levels of genes associated with the TLR/NF-κB signaling pathway in the lung and intestinal tissues were determined by reverse transcription-quantitative polymerase chain reaction. The results of the present study indicated that, in the rat model of allergic asthma complicated with intestinal flora disorder, the expression levels of IL-4 and IgE, and the numbers of inflammatory cells and C. albicans increased, and marked inflammatory cell infiltration was observed in lung tissues, suggesting that the animal model was successfully established. Furthermore, the present results revealed the mRNA expression levels of genes associated with the TLR/NF-κB signaling (including myeloid differentiation primary response 88, TNF receptor associated factor 6 and β-arrestin) were upregulated in both of the lung and intestinal tissues of the model group rats. Collectively, the results demonstrated that the TLR/NF-κB signaling may serve roles in the mutual interactions between the lung and the large intestine, and TLR and NF-κB may be potential targets for the treatment of lung diseases complicated with intestinal disorders.

Allergen immunotherapy modulates sensitivity of Treg cells to apoptosis in a rat model of allergic asthma.

To study the apoptosis of Foxp3+ Treg cells following Alstonia scholaris pollen sensitization-challenge and following allergen immunotherapy. Wistar rats were sensitized-challenged with Alstonia scholaris pollen and were further given intranasal immunotherapy. For the analysis of the apoptotic proteins on Treg cells by flow cytometry, multiple gating procedures were followed. Allergen sensitization-challenge increases Annexin-V, Fas, FasL, caspases-8, 9, 3 cytochrome-C, APAF-1, Bax, perforin-1 and granzyme-B on Treg cells which is decreased following intranasal immunotherapy. On the other hand, Bcl-2 expression is decreased in allergy and increased by immunotherapy. Apoptosis of Treg cells is increased following allergen sensitization-challenge via extrinsic, intrinsic and perforin/granzyme pathways and allergen immunotherapy decreased the sensitivity to apoptosis of Treg cells.

Ligustrazine improves blood circulation by suppressing Platelet activation in a rat model of allergic asthma

Chuan-xiong (Ligusticum wallichii) is a traditional herbal medicine in Eastern Asia, but the effect of its active component ligustrazine remains unclear. We explored its effect and possible mechanism in a well-characterized rat model of allergic asthma. Ligustrazine suppressed bronchial hyper-responsiveness to methacholine, and suppressed lung inflammation in asthmatic rats. Ligustrazine exhibited potent immuno-modulatory and anti-inflammatory effects: it suppressed lymphocyte and eosinophil mobilization, and reduced cytokine IL-5 and IL-13 production significantly in lung tissues from asthmatic rats (P<0.05). Further histological examinations clearly demonstrated that ligustrazine improved blood circulation and ameliorated platelet activation, aggregation and adhesion, which induced sustained infiltration and activation of various inflammatory cells, including lymphocytes and eosinophils, followed by synthesis and release of a variety of pro-inflammatory mediators and cytokines. The present study suggests that ligustrazine is a potent agent for the treatment of allergic asthma due to its strong anti-inflammatory and immuno-modulatory properties.

Isotonic Saline Subjected to Taylor-Couette-Poiseuille Flow Demonstrates Anti-Inflammatory Activity in a Rat Model of Allergic Asthma

Isotonic Saline Subjected to Taylor-Couette-Poiseuille Flow Demonstrates Anti-Inflammatory Activity in a Rat Model of Allergic Asthma

Anti‐Inflammatory, Immunomodulatory, and Heme Oxygenase‐1 Inhibitory Activities of Ravan Napas, a Formulation of Uighur Traditional Medicine, in a Rat Model of Allergic Asthma

Ravan Napas (RN) is a traditional formula used to treat pulmonary symptoms and diseases such as coughing, breathing difficulty, and asthma in traditional Uighur medicine. The purpose of this study was to investigate the anti-inflammatory, and immuno-modulatory activity of RN in a well-characterized animal model of allergic asthma. Rats were sensitized with intraperitoneal (ip) ovalbumin (OVA) and alum, and then challenged with OVA aerosols. The asthma model rats were treated with RN; saline- and dexamethasone- (DXM-) treated rats served as normal and model controls. The bronchoalveolar lavage fluid (BALF) cellular differential and the concentrations of sICAM-1, IL-4, IL-5, TNF-α, INF-γ, and IgE in serum were measured. Lung sections underwent histological analysis. The immunohistochemistry S-P method was used to measure the expression of ICAM-1 and HO-1 in the lung. RN significantly reduced the number of inflammatory cells in BALF and lung tissues, decreased sICAM-1, IL-4, IL-5, TNF-α, and IgE in serum, and increased serum INF-γ. There was a marked suppression of ICAM-1 and HO-1 expression in the lung. Our results suggest that RN may have an anti-inflammatory and immuneregulatory effect on allergic bronchial asthma by modulating the balance between Th1/Th2 cytokines.

Effects of antisense interleukin‐5 gene transferred by recombinant adeno‐associated virus to allergic rats

The accumulation of eosinophils in airways is an important characteristic of asthma. The process is primarily mediated by interleukin-5 (IL-5) secreted by Th2 lymphocytes. This study explored a new approach to asthma therapy in which allergic rats were transfected with the IL-5 antisense gene delivered by the recombinant adeno-associated virus (rAAV-ASIL-5). The viral vector rAAV-ASIL-5 was constructed and the IL-5 antisense gene transfected into allergic rats. The levels of IL-5, IgE, eotaxin and eosinophilic cationic protein (ECP) in sera and bronchoalveolar lavage fluid (BALF) were measured by ELISA. The inflammatory responses in lung tissues were evaluated by histological study. The levels of IL-5 protein in serum and BALF were significantly decreased in the allergic rats treated with rAAV-ASIL-5 (P < 0.05). Serum ovalbumin-specific IgE was reduced in treated rats compared with untreated rats (P < 0.05). rAAV-ASIL-5 treatment also reduced eosinophils in the peripheral blood and BALF, as well as the ECP and eotaxin levels in serum and BALF (P < 0.05). There was significantly less inflammation in the lungs of rAAV-ASIL-5-treated rats than in those of untreated rats. No obvious pathological damage to the kidneys and livers of the rats treated with rAAV was observed. Treatment with rAAV-ASIL-5 inhibited the accumulation of eosinophils and airway inflammation in the rat model of allergic asthma by suppressing IL-5 production. These results suggest that rAAV-ASIL-5-based gene therapy may be used for the treatment of allergic asthma.

The effects of repeated allergen challenge on airway smooth muscle structural and molecular remodeling in a rat model of allergic asthma

The effects of remodeling of airway smooth muscle (SM) by hyperplasia on airway SM contractility in vivo are poorly explored. The aim of this study was to investigate the relationship between allergen-induced airway SM hyperplasia and its contractile phenotype. Brown Norway rats were sensitized with ovalbumin (OVA) or saline on day 0 and then either OVA-challenged once on day 14 and killed 24 h later or OVA-challenged 3 times (on days 14, 19, and 24) and killed 2 or 7 days later. Changes in SM mass, expression of total myosin, SM myosin heavy chain fast isoform (SM-B) and myosin light chain kinase (MLCK), tracheal contractions ex vivo, and airway responsiveness to methacholine (MCh) in vivo were assessed. One day after a single OVA challenge, the number of SM cells positive for PCNA was greater than for control animals, whereas the SM mass, contractile phenotype, and tracheal contractility were unchanged. Two days after three challenges, SM mass and PCNA immunoreactive cells were increased (3- and 10-fold, respectively; P < 0.05), but airway responsiveness to MCh was unaffected. Lower expression in total myosin, SM-B, and MLCK was observed at the mRNA level (P < 0.05), and total myosin and MLCK expression were lower at the protein level (P < 0.05) after normalization for SM mass. Normalized tracheal SM force generation was also significantly lower 2 days after repeated challenges (P < 0.05). Seven days after repeated challenges, features of remodeling were restored toward control levels. Allergen-induced hyperplasia of SM cells was associated with a loss of contractile phenotype, which was offset by the increase in mass.

The effects of anti-sense interleukin-5 gene transferred by recombinant adeno-associated virus in allergic rats

AbstractThe accumulation and infiltration of eosinophils in airways is one of the most important characteristics of asthma, and is mediated partly by secretion of IL-5 from Th2 lymphocytes. It is well known that interleukin-5 (IL-5) played an important role in the regulation of eosinophils. In this study, an anti-sense IL-5 gene transferred by recombinant adeno-associated virus (rAAV-ASIL-5) was prepared to transfect allergic rats. It was found that the expression of IL-5 protein in plasma and BALF were inhibited significantly. The rAAV-ASIL-5-mediated suppression of total cell counts in peripheral blood and BALF were also observed. Moreover, rAAV-ASIL-5 remarkably reduced the eosinophil counts in peripheral blood and BALF, as well as the expression of ECP protein in plasma and BALF. The inflammation in lungs of rAAV-ASIL-5 pretreated rats also became slighter when compared with allergic rats. Otherwise, no apparent pathological damage to vital organs of rats was found. In conclusion, recombinant adeno-associated virus-mediated delivery of anti-sense IL-5 gene inhibited the accumulation of eosinophils and the airways inflammation in rat model of allergic asthma via suppressing IL-5 expression. It suggested the feasibility of rAAV-ASIL-5 in the gene therapy for allergic asthma and other eosinophilic diseases.

Acute effect of methylprednisolone on the brain in a rat model of allergic asthma

Asthma affects not only the airways but also the central nervous system (CNS). Corticosteroids are an effective therapeutic agents for asthma. In our study, we investigated the acute effect of ovalbumin (OVA) on the brain and the effectiveness of methylprednisolone (MP) in both the periphery and CNS in a rat model of allergic asthma. Rats sensitized to OVA and exposed to OVA aerosol challenge to induce allergic asthma were compared with control rats and rats sensitized to OVA and pretreated with MP before OVA exposure. In response to OVA stimulation, the amount of c-Fos and glial fibrillary acidic protein (GFAP) increased, while that of neuronal nitric oxide synthase (nNOS) decreased in the nucleus tractus solitarius (NTS). In addition, the c-Fos, GFAP, and nNOS levels in the hippocampus and the nNOS levels in the olfactory bulb increased. However, the expression of these proteins in the frontal and cerebellar cortices was not affected by OVA stimulation. In contrast, pretreatment with MP before OVA exposure decreased the protein expression of c-Fos in the CA1 area, GFAP in NTS, and nNOS in CA1 and olfactory bulb, and while it increased the nNOS content in the NTS. These findings suggest that the brain responds to OVA stimulation in a rat model of allergic asthma and that MP treatment cannot only ameliorate airway inflammation but also OVA-induced effects.

Estrogen Receptor β: Expression Profile and Possible Anti-Inflammatory Role in Disease

Estrogen receptor (ER) beta agonists have been demonstrated to possess anti-inflammatory properties in inflammatory disease models. The objective of this study was to determine whether ERbeta agonists affect in vitro and in vivo preclinical models of asthma. mRNA expression assays were validated in human and rodent tissue panels. These assays were then used to measure expression in human cells and our characterized rat model of allergic asthma. ERB-041 [7-ethenyl-2-(3-fluoro-4-hydroxyphenyl)-1,3-benzoxazol-5-ol], an ERbeta agonist, was profiled on cytokine release from interleukin-1beta-stimulated human airway smooth muscle (HASM) cells and in the rodent asthma model. Although ERbeta expression was demonstrated at the gene and protein level in HASM cells, the agonist failed to have an impact on the inflammatory response. Similarly, in vivo, we observed temporal modulation of ERbeta expression after antigen challenge. However, the agonist failed to have an impact on the model endpoints such as airway inflammation, even though plasma levels reflected linear compound exposure and was associated with an increase in receptor activation after drug administration. In these modeling systems of airway inflammation, an ERbeta agonist was ineffective. Although ERbeta agonists are anti-inflammatory in certain models, this novel study would suggest that they would not be clinically useful in the treatment of asthma.

Effect Of Cetirizine On Early- And Late-phase Airway Responses In A Brown Norway Rat Model Of Allergic Asthma

Effect Of Cetirizine On Early- And Late-phase Airway Responses In A Brown Norway Rat Model Of Allergic Asthma

Effects of oral alpha‐tocopherol on lung response in rat model of allergic asthma

Asthma is a chronic inflammatory disease in which an oxidant/antioxidant imbalance plays an important role. d-alpha-tocopherol (biologically the most active form of vitamin E) has redox properties and by scavenging the free radicals can act as an antioxidant. The aim of this study was to examine the effects of orally administered alpha-tocopherol in a rat model of allergic asthma. Actively sensitized rats (OA) were treated with alpha-tocopherol (400 mg/kg/day for 10 days) or vehicle; 1 h after the last dose, they were challenged with antigen aerosol. The antigen-induced airway hyperresponsiveness to direct bronchoconstrictor (serotonin), the inflammatory cell infiltrate and histological changes were determined 1 or 24 h after the antigen challenge. Alpha-tocopherol pretreatment was not significantly effective at reducing the studied parameters when compared with controls, even though there was a tendency to a reduction in bronchial responsiveness and in eosinophil and neutrophil infiltration. Alpha-tocopherol when administered in the chosen study design in an animal model of asthma had no major effect on airway inflammation. The effect of antioxidants deserves further evaluation.