Ovalbumin-sensitized Rats Research Articles

NButGT Reinforces the Beneficial Effects of Epinephrine on Cardiac Mitochondrial Respiration, Lactatemia and Cardiac Output in Experimental Anaphylactic Shock.

Anaphylactic shock (AS) is the most severe form of acute systemic hypersensitivity reaction. Although epinephrine can restore patients' hemodynamics, it might also be harmful, supporting the need for adjuvant treatment. We therefore investigated whether NButGT, enhancing O-GlcNAcylation and showing beneficial effects in acute heart failure might improve AS therapy. Ovalbumin-sensitized rats were randomly allocated to six groups: control (CON), shock (AS), shock treated with NButGT alone before (AS+pre-Nbut) or after (AS+post-Nbut) AS onset, shock treated with epinephrine alone (AS+EPI) and shock group treated with combination of epinephrine and NButGT (AS+EPI+preNBut). Induction of shock was performed with an intravenous (IV) ovalbumin. Cardiac protein and cycling enzymes O-GlcNAcylation levels, mean arterial pressure (MAP), heart rate, cardiac output (CO), left ventricle shortening fraction (LVSF), mitochondrial respiration, and lactatemia were evaluated using Western blotting experiments, invasive arterial monitoring, echocardiography, mitochondrial oximetry and arterial blood samples. AS decreased MAP (-77%, p < 0.001), CO (-90%, p < 0.001) and LVSF (-30%, p < 0.05). Epinephrine improved these parameters and, in particular, rats did not die in 15 min. But, cardiac mitochondrial respiration remained impaired (complexes I + II -29%, p < 0.05 and II -40%, p < 0.001) with hyperlactatemia. NButGT pretreatment (AS+pre-Nbut) efficiently increased cardiac O-GlcNAcylation level as compared to the AS+post-Nbut group. Compared to epinephrine alone, the adjunction of NButGT significantly improved CO, LVSF and mitochondrial respiration. MAP was not significantly increased but lactatemia decreased more markedly. Pretreatment with NButGT increases O-GlcNAcylation of cardiac proteins and has an additive effect on epinephrine, improving cardiac output and mitochondrial respiration and decreasing blood lactate levels. This new therapy might be useful when the risk of AS cannot be avoided.

Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats

Objective: To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats. Methods: Rats were randomly divided into six groups: the control group, the asthmatic group, and the asthmatic groups treated with dexamethasone (1 mg/kg; oral gavage) or three doses of rosmarinic acid (0.5, 1, and 2 mg/kg; oral gavage). For induction of asthma, rats received intraperitoneal injections and inhalation of ovalbumin. After 21 days, bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses. Moreover, total and differential white blood cell counts were determined. Results: The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group. In addition, rosmarinic acid reduced white blood cell count and the percentages of eosinophils, monocytes, and neutrophils while increasing the percentage of lymphocytes. Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid. Conclusions: Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.

Effect of Allium cepa extract on total and differential WBC, TP level, oxidant and antioxidant biomarkers, and lung pathology in ovalbumin-sensitized rats.

Previous studies have shown that Allium cepa (A. cepa) has relaxant and anti-inflammatory effects. In this research, A. cepa extract was examined for its prophylactic effect on lung inflammation and oxidative stress in sensitized rats. Total and differential white blood cell (WBC) count in the blood, serum levels of oxidant and antioxidant biomarkers, total protein (TP) in bronchoalveolar lavage fluid (BALF), and lung pathology were investigated in control group (C), sensitized group (S), and sensitized groups treated with A. cepa and dexamethasone. Total and most differential WBC count, TP, NO2, NO3, MDA (malondialdehyde), and lung pathological scores were increased while lymphocytes, superoxide dismutase (SOD), catalase (CAT), and thiol were decreased in sensitized animals compared to controls (p < 0.01 to p < 0.001). Treatment with all concentrations of extract significantly improved total WBC, TP, NO2, NO3, interstitial fibrosis, and emphysema compared to the S group (p < 0.05 to p < 0.001). Two higher concentrations of the extract significantly decreased neutrophil and monocyte count, malondialdehyde, bleeding and epithelial damage but increased lymphocyte, CAT, and thiol compared to the S group (p < 0.05 to p < 0.001). Dexamethasone treatment also substantially improved most measured parameters (p < 0.05 to p < 0.001), but it did not change eosinophil percentage. It was proposed that A. cepa extract could affect lung inflammation and oxidative stress in sensitized rats.

Inhibition of oxidative stress, IL-13, and WNT/β-catenin in ovalbumin-sensitized rats by a novel organogel of Punica granatum seed oil saponifiable fraction

Bronchial asthma is a chronic inflammatory disease marked by inflammation, oxidative stress, and structural remodeling. Here, we prepared two pomegranate fractions from the seed oil, saponifiable (Sap) and unsaponifiable (UnSap). Two organogels (Orgs) were also formulated with the Sap (Org1) or the UnSap (Org2) fraction and beeswax (BW). All preparations were evaluated in vitro for their antioxidant and anti-inflammatory impacts. The transdermal delivery of the most efficient one was evaluated against ovalbumin (OV)-induced bronchial asthma in rats compared to dexamethasone (DEX). The results showed that the prepared pomegranate fractions and BW had considerable amounts of phenolics (flavonoids and tannins) and triterpenoids. Org1 was shown to be the most effective antioxidant and anti-inflammatory fraction with synergistic activities (combination index, 1), as well as having protective and therapeutic influences on OV-sensitized rats. Org1 inhibited the multiple OV-induced signaling pathways, comprising ROS, WNT/β-catenin, and AKT, with an efficiency superior to DEX. Subsequently, the pro-inflammatory (COX-2, NO, and IL-13), and pro-fibrotic (COL1A1) mediators, oxidative stress, and mucin secretion, were all down-regulated. These outcomes were verified by the histopathological results of lung tissue. Collectively, these outcomes suggest that the transdermal delivery of Org1 to OV-sensitized rats shows promise in the protection and treatment of the pathological hallmarks of asthma.

Altered gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine levels in lung tissue of obese ovalbumin-sensitized rats

AimsThe association between asthma and obesity has been shown but its accurate mechanism is unknown. In the current study, we sought to investigate the gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine level (IL-6, IL-1β, and TNF-α) in obese Ovalbumin (OVA)-sensitized female and male Wistar rats lung tissue. Main methodsAnimals in both males and females were divided into eight groups (four groups in each sex) based on diet and OVA-sensitization: normal diet, a normal diet with OVA-sensitization, high-fat diet (HFD), and OVA-sensitization with an HFD. Key findingsIn both sexes, obese OVA-sensitized rats, the methacholine concentration-response curve shifted to the left and EC50 methacholine decreased. Increased pro-inflammatory cytokines as well as elevated IL-17/TRAF6/MAPK axis genes and decreased USP25 gene expression were identified in obese OVA-sensitized groups. SignificanceThe results indicate that in obese OVA-sensitized rats, the IL-17 axis were involved in the pathogenesis of the disease and can be considered as a therapeutic target in subjects with obesity-related asthma.

Immunomodulatory and anti-inflammatory effects of N-acetylcysteine in ovalbumin-sensitized rats

BackgroundPro-inflammatory cytokines such as interleukin-5 (IL-5) and tumor necrosis factor-alpha (TNF-α) as well as immunoglobulin-E (IgE) appear to play a role in asthma. N-acetylcysteine (NAC), an antioxidant, might have clinical benefits in asthma prevention. The possible preventive effects of NAC against experimentally induced asthma in rats are investigated. The rats were allocated into five groups: a normal control, asthma control, a standard dexamethasone (DEXA, 1 mg/kg, orally) group, and two NAC groups (300 and 500 mg/kg, orally, respectively). Ovalbumin (OVA) sensitization was used to trigger asthma, which was then followed by an intra-nasal challenge. Test gents were administrated for 14 days before the challenge and during the three challenge days (20, 21, and 22). The tidal volume (TV) and peak expiratory flow rate (PEFR) as respiratory functions were determined. The pro-inflammatory cytokines as IL-5 and TNF-α were evaluated in lung homogenate. Serum IgE and absolute eosinophil count (AEC) in bronchoalveolar lavage fluid (BALF) were measured. In addition, the oxidative markers in lung tissue and nitrosative marker in BALF were assessed; finally, lungs were isolated for histopathological study.ResultsNAC restored lung functions, inhibited the asthma-dependent increase in TNF-α, IL-5, IgE, AEC, nitric oxide, and malondialdehyde levels. NAC further re-established lung glutathione content and superoxide dismutase activity, resulting in milder overall lung pathology.ConclusionsExperimental bronchial asthma may be protected by NAC. The anti-asthmatic potential of NAC may be explained by its suppressant influence on IgE antibody formation, pro-inflammatory cytokines production, eosinophil infiltration, and oxidative stress.

Evaluation of inflammatory miRNA155 and 146a expression in heart tissue of ovalbumin-sensitized male rats

Introduction: Asthma is a chronic pulmonary inflammation occurred in response to different allergens, leading to respiratory system insufficiency. The production of different inflammatory factors and enhanced immune system response may affect the function of other organs. The aim of this study was to investigate the expression of inflammatory microRNAs in cardiac tissue in asthmatic rat model. Methods: In this study, the animals were allocated into Control and Asthmatic rats (n=8). To induce asthma, rats were challenged with ovalbumin. 14 days after induction of asthma, rats were euthanized and Hematoxylin-Eosin staining was performed to assess pathological changes in pulmonary tissue. Serum levels of cardiac enzymes were measured using ELISA kits. Finally, transcription level of inflammatory miRNAs, miRNA-146a and -155, were measured using real-time PCR analysis. Results: Based on our findings, histological examination indicated the existence of pathological changes in pulmonary tissue after asthma induction. Bright-field analysis revealed an existence of inflammatory response and cytotoxicity in cardiac tissue. Also, the serum levels of CpK-MB, ALT, and AST were significantly higher in the serum of asthmatic group compared to control group (p&lt;0.05). Finally, asthmatic condition induced the expression of (2-fold) miRNA-146a and (1.5-fold)-155 in cardiac tissue, respectively. Conclusion: As a conclusion, it could be concluded that asthmatic condition induces systemic inflammation in cardiac tissue. On a more general note, we propose that therapeutical approaches directed to inflammatory pathway may be required to preserve cardiac injuries caused of asthma.

C-kit+ cells offer hopes in ameliorating asthmatic pathologies via regulation of miRNA-133 and miRNA-126.

Objective(s):There are still challenges regarding c-kit+ cells’ therapeutic outcome in the clinical setting. Here, we examined the c-kit+ cell effect on the alleviation of asthma by modulating miRNAs expression.Materials and Methods:To induce asthma, male rats were exposed to ovalbumin. Bone marrow-derived c-kit+ cells were enriched by MACS. Animals were classified into four groups (6 rats each). Control rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally containing 3×105 c-kit+ and c-kit- cells. Cells were stained with Dil fluorescent dye to track in vivo condition. Pathological changes were monitored in asthmatic rats after transplantation of c-kit+ and c-kit- cells. Serum levels of IL-4 and INF-γ were measured by ELISA. Transcription of miRNAs (-126 and 133) was assessed by real-time PCR analysis.Results:Pathological examination and Th1 and Th2 associated cytokine fluctuation confirmed the occurrence of asthma in rats indicated by chronic changes and prominent inflammation compared with the control group (P<0.05). Both c-kit+ and c-kit- cells were verified in pulmonary niche. Administration of c-kit positive cells had the potential to change INF-γ/IL-4 ratio close to the normal values compared with matched-control asthmatic rats (P<0.05). We also found that c-kit+ cells regulated the expression of miRNA-126 and -133, indicated by an increase of miRNA-133 and decrease of miRNA-126 compared with cell-free sensitized groups (P<0.05). Conclusion:c-kit- cells were unable to promote any therapeutic outcomes in the asthmatic milieu. c-kit+ cells had the potential to diminish asthma-related pathologies presumably by controlling the transcription of miRNA-126 and -133.

Treadmill exercise ameliorates memory deficits and hippocampal inflammation in ovalbumin-sensitized juvenile rats

The behavioral changes, including spatial learning and memory impairment as well as depressive- and anxiety-like behaviors in an animal model of asthma were demonstrated previously. On the other hand, there is increasing evidence that the anti-inflammatory actions of exercise are related to their neuroprotective properties against different insults in the brain. This study was aimed to explore the effects of moderate treadmill exercise on cognitive deficits and possible anti-inflammatory mechanisms in ovalbumin (OVA)-sensitized rats. The exercise groups were trained to run on the treadmill 30 min/day with an intensity of 12 m/min, 5 days/week for 4 weeks. Animals in the OVA groups were sensitized by two intraperitoneal (i.p.) injections of OVA (10 μg/injection) and challenged with OVA by inhalation during the treadmill running exercise period. Passive avoidance (PA) memory, levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α in the hippocampus, total and differential white blood cell (WBC) count in the blood as well as pathological changes of the lung were then evaluated. OVA-sensitization was resulted in cognitive deficits in the PA task, along with increased total and differential WBC in blood and TNF-α in the hippocampus. However, exercise ameliorated these changes and increased the IL-10 level in the hippocampus, suggesting that moderate treadmill exercise can improve memory impairment in OVA-sensitized rats due to its anti-inflammatory properties.

Chitosan Hydrogel Doped with PEG-PLA Nanoparticles for the Local Delivery of miRNA-146a to Treat Allergic Rhinitis.

To prepare a binary formulation delivering miRNA-146 and evaluate a nucleic acid nasal delivery system by investigating its pharmacodynamic effects in allergic rhinitis. The gel/NPs/miR-146a thermosensitive in situ chitosan hydrogel carrying a nucleic acid was prepared and evaluated for its characteristics, including temperature sensitivity, gel strength, mucosal adhesion and drug release profile. After nasal administration of the formulation to ovalbumin-sensitized rats, the treatment of allergic rhinitis was verified by assessing nasal symptoms, hematology, hematoxylin-eosin (HE) staining and immunohistochemistry. Western Blot(WB) was used to analyze nasal inflammatory factors as well as miRNA-146-related factors, and the miR146 expression level was measured by PCR. Subsequently, the effects of the gel/NPs/miR-146a binary formulation were evaluated for the nasal delivery of nucleic acids in rhinitis therapy. The prepared binary formulation quickly formed a gel in the nasal cavity at a temperature of 34 °C with good mucosal adhesion, which delivered nucleic acids into the nasal mucosa stably and continuously. Gel/NPs/miR-146a was able to sustain the delivery of miRNA into the mucosa after nasal administration. When compared with the monolithic formulations, the gel/NPs/miR-146a binary formulation performed better regarding its nucleic acid delivery ability and pharmacodynamic effects. The gel/NPs/miR-146a binary preparation has a suitable nasal mucosal drug delivery ability and has a positive pharmacodynamic effect for the treatment of ovalbumin-induced rhinitis in rats. It can serve as a potential nucleic acid delivery platform for the treatment of allergic rhinitis.

Effect of moxibustion at Feishu (BL 13) on airway inflammation in asthma model rats

To observe the effect of moxibustion at Feishu (BL 13) on related inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid of asthma model rats, and to explore the mechanism of moxibustion in treating asthma. A total of 48 Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, a moxibustion group and a medication group, with 12 rats in each group. Except for the normal group, the rats in the other three groups were subjected to ovalbumin sensitization to stimulate the asthma. At the same time, rats in the moxibustion group received moxibustion at bilateral Feishu (BL 13), and rats in the medication group received dexamethasone by intragastric administration. Rats in the normal and the model groups only received the same fixation and normal saline by intragastric administration. After the interventions, the inspiratory resistance, the expiratory resistance, and the pulmonary compliance were measured for rats in each group; the numbers of the inflammatory cells in the bronchoalveolar lavage fluid were counted; the levels of the involved inflammatory factors in bronchoalveolar lavage fluid were detected; the pathological morphologies of the lung tissues were observed under light microscope. After modeling, compared with the normal group, the rats in the model group showed obvious asthma attack-like response, significantly increased inspiratory resistance and expiratory resistance (both P 0.05). Both moxibustion at Feishu (BL 13) and intragastric administration of dexamethasone can improve the asthma attack-like symptoms of ovalbumin-sensitized rats; regulating the inflammatory cell numbers and the inflammatory factor contents in the lung may be one mechanism of moxibustion in treating asthma.

Treadmill exercise restores memory and hippocampal synaptic plasticity impairments in ovalbumin-sensitized juvenile rats: Involvement of brain-derived neurotrophic factor (BDNF)

Studies demonstrate that asthma, especially during childhood, affects the functions of the brain including learning and memory. Exercise is well known for its neuroprotective functions and for its beneficial effects on asthma. We aimed to assess the effects of exercise on cognitive function, synaptic plasticity, and hippocampal brain-derived neurotrophic factor (BDNF) levels in ovalbumin (OVA) sensitized juvenile rats. Rats were sensitized by intraperitoneal administration and inhaled OVA. Animals were subjected to treadmill running exercise during the OVA-challenged period. T-helper type 2 (Th2) cytokine [interleukin (IL)-4], Th1 cytokine (INF-γ) levels, and INF-γ/IL-4 (Th1/Th2) ratio in bronchoalveolar lavage fluid (BALF), and tracheal response to methacholine and OVA were measured. Further, memory behaviors and BDNF levels were measured in the hippocampus as well as long-term potentiation (LTP) was assessed by recording field excitatory postsynaptic potentials (fEPSPs) in the hippocampus. The levels of IL-4 and TGF-β were decreased but INF-γ level and INF-γ/IL-4 ratio increased in the BALF due to exercise in the OVA-sensitized animals. In addition, exercise improved OVA-sensitization induced cognitive impairments, increased BDNF levels, and enhanced hippocampal LTP in OVA-sensitized rats. Exercise is not only effective in the alleviation of airway inflammation by restoring Th1/Th2 cytokines balance, but also is a candidate for improvement of memory and synaptic plasticity deficits partially through increasing the levels of hippocampal BDNF in OVA-sensitized rats.

Treatment with a platelet-activating factor receptor antagonist improves hemodynamics and reduces epinephrine requirements, in a lethal rodent model of anaphylactic shock.

In some cases, anaphylactic shock (AS) is still lethal, despite rapid use of epinephrine. High doses of epinephrine are associated with severe complications. Platelet-activating factor (PAF) is secreted in massive amounts during AS, and a high plasma level is correlated with increased AS severity. To assess the effect of ABT-491, a PAF-receptor antagonist and possible adjunct treatment, alone or in combination with epinephrine during AS. AS was induced by intravenous injection of 1mg ovalbumin into ovalbumin-sensitized rats. Rats were then randomly assigned to 5 groups (n=10 per group): SHAM (vehicle only), SHOCK (no treatment), ABT (ABT-491 1mg/kg), EPI (epinephrine 5µg as a bolus then 10µgkg-1 min-1 by continuous infusion, followed by a reducing protocol) and EPI-ABT (both treatments). Ovalbumin injection resulted in a severe decrease in mean arterial pressure, left ventricular inotropy (max dP/dt) and left ventricular shortening fraction (LVSF). All rats from the ABT group survived until the end of the experiment. ABT-491 prevented the LVSF decrease observed in the SHOCK group (at T15: ABT 50%±11% vs SHOCK 36%±9%, P=.01), significantly reduced the dose of epinephrine needed to treat anaphylactic shock (EPI-ABT 314±67µg/kg vs EPI 475±69µg/kg, P<.001) and reduced the time to restore basal MAP (ABT 23±7minutes vs EPI-ABT 13±5minutes, P<.01). AS was characterized by early cardiac dysfunction in our model. Treatment with ABT-491 allowed survival until the end of the experiment and reduced cardiac dysfunction. Use of the PAF-R antagonist had a synergistic effect with epinephrine and allowed a significant reduction in epinephrine consumption. Use of PAF-R antagonists during AS could reduce epinephrine-related complications and improve the treatment of epinephrine refractory cases.

Alpha-linolenic acid ameliorates bronchial asthma features in ovalbumin-sensitized rats.

Effect of alpha-linolenic acid (ALA) against ovalbumin (OVA)-induced inflammation, oxidant/antioxidant imbalance and pathological features was examined in rat. Total and differential WBC count and oxidant/antioxidant levels in BALF (bronchoalveolar lavage fluid) as well as lung pathological features were investigated in five groups of rats including controls (group C), rats sensitized with OVA (group S) and S treated with either ALA (0.2 and 0.4mg/ml) or dexamethasone. As compared to group C, in OVA-sensitized rats, increases in WBC counts, levels of oxidant biomarkers and most pathological scores were observed while lymphocyte percentage and antioxidants levels decreased. Treatment with ALA (0.2 and 0.4mg/ml) significantly reduced total WBC, NO2 and NO3 levels, interstitial fibrosis and emphysema compared to sensitized group. The higher dose of ALA also significantly decreased neutrophil, eosinophil, and monocyte counts, MDA levels and interstitial inflammation but increased lymphocyte counts, as well as antioxidants levels, compared to sensitized group. Dexamethasone administration led to a significant improvement of most factors compared to group S but had no effects on total WBC count, bleeding and epithelial damage. Alpha-linolenic acid suppressed inflammation and oxidative stress, making it a potential therapeutic candidate for treatment of airway inflammatory diseases such as bronchial asthma.

Cellular and Immunohistochemical Changes in Anaphylactic Shock Induced in the Ovalbumin-Sensitized Wistar Rat Model.

Anaphylactic shock (AS) is a life-threatening, multisystem disorder arising from sudden release of mast cell- and basophil-derived mediators into the circulation. In this study, we have used a Wistar rat model to investigate AS-associated histopathologic changes in various organs. Rats were sensitized with ovalbumin (1 mg s.c), and AS was induced by intravenous injection of ovalbumin (1 mg). Experimental groups included nonallergic rats (n = 6) and allergic rats (n = 6). Heart rate and blood pressure were monitored during one hour. Organs were harvested at the end of the experiment and prepared for histologic and immunohistochemical studies. Lung, small bowel mucosa and spleen were found to undergo heavy infiltration by mast cells and eosinophils, with less prominent mast cell infiltration of cardiac tissue. The mast cells in lung, small bowel and spleen exhibited increased expression of tryptase, c-kit and induced nitric oxide synthase (iNOS). Increased expression of endothelial nitric oxide synthase (eNOS) by vascular endothelial cells was noted principally in lung, heart and small bowel wall. The Wistar rat model of AS exhibited accumulation of mast cells and eosinophils in the lung, small bowel, and spleen to a greater extent than in the heart. We conclude that lung and gut are principal inflammatory targets in AS, and likely contribute to the severe hypotension of AS. Targeting nitric oxide (NO) production may help reduce AS mortality.

Hydro-ethanolic extract of Curcuma longa affects tracheal responsiveness and lung pathology in ovalbumin-sensitized rats.

Anti-inflammatory effect of Curcuma longa (C. longa) was shown previously. In the present study, the effect of the plant on tracheal responsiveness and lung pathological features in ovalbumin-sensitized rats was evaluated. Six groups of rats including control (C), ovalbumin (OVA)-sensitized (S), S groups treated with C. longa (CL; 0.75, 1.50, and 3.00 mg/ml equal to 150, 300 and 600 mg/kg/day) and dexamethasone (D; 1.25 μg/ml) were studied (n=8 in each group). The extract of C. longa and dexamethasone were administered with daily drinking water of animals during sensitization period (for 21 days). Following the treatment period, tracheal responsiveness to methacholine and ovalbumin and lung pathological features was investigated. Tracheal responsiveness to methacholine and OVA and lung pathological scores were increased in group S compared to controls (p<0.01 to p<0.001); however, these parameters in groups treated with dexamethasone and two higher concentrations of C. longa were significantly decreased compared to group S (p<0.05 to p<0.001). Tracheal responsiveness to methacholine was decreased from 50 to 400% due to the extract treatment. All concentrations of C. longa significantly decreased interstitial fibrosis compared to group S (p<0.05 to p<0.001). Treatment with the extract resulted to improvement of pathological changes from 20 to 70%. These results showed a preventive effect for C. longa extract on tracheal responsiveness and lung pathological insults in sensitized rats which were similar or even more than those of dexamethasone at used concentrations.

Metabolomics analysis of baicalin on ovalbumin-sensitized allergic rhinitis rats.

Allergic rhinitis (AR) is a global health problem that appears in all age groups and affects approximately 15–30% of people. Baicalin has been used for the treatment of various allergic diseases, including AR. However, the metabolic mechanisms of AR and baicalin against AR have not been systematically studied. Here, ovalbumin-sensitized AR rats were used as a model, and animal behaviour, histological analysis, enzyme-linked immunosorbent assay (ELISA) and metabolomics were used to elucidate the mechanism of baicalin for AR. The results indicated that baicalin has a protective effect on AR rats by inhibiting the release of immunoglobulin E (IgE), histamine, interleukin-1 beta (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α). In addition, ovalbumin-induced AR included modulation of arachidonic acid, leukotriene A4 (LTA4), leukotriene B4 (LTB4), α-ketoglutaric acid, phosphatidylcholine PC (20 : 4/0 : 0), PC (16 : 0/0 : 0), citric acid, fumarate, malate, 3-methylhistidine, histamine and other amino acids that are involved in arachidonic acid, histidine metabolism, the TCA cycle and amino acid metabolism. Thus, AR could be alleviated or reversed by baicalin.

The Effects of Ocimum basilicum Extract and Its Constituent, Rosmarinic Acid on Total and Differential Blood WBC, Serum Levels of NO, MDA, Thiol, SOD, and CAT in Ovalbumin Sensitized Rats.

The effects of Ocimum basilicum (O. basilicum) and its constituent, rosmarinic acid, on total and differential blood WBC, serum levels of NO2, NO3, MDA, thiol, SOD, and CAT in sensitized rats were examined. The study was performed in control animals (group C) and eight groups of sensitized rats to ovalbumin which were given drinking water alone (group S), drinking water containing three concentrations of O. basilicum (O; 0.75, 1.5 and 3.0 mg/mL), three concentrations of rosmarinic acid (R; 0.125, 0.25 and 0.5 mg/mL) and dexamethasone (1.25 μg/mL), (n = 6 for R treated and n = 8 for other groups). Total and differential WBC as well as serum concentrations of oxidant and antioxidant biomarkers were measured in all groups. Serum levels of oxidant biomarkers, total WBC count, percentages of eosinophils and neutrophils were significantly increased but other measured parameters except monocytes were significantly decreased in group S compared to group C. Serum levels of oxidant biomarkers, total WBC count, percentages of eosinophils, neutrophils and monocytes were significantly decreased but other measured parameters were significantly increased in treated S groups with dexamethasone, extract, and rosmarinic acid compared to group S. The effects of the extract and rosmarinic acid on some measured variables were significantly higher than the effect of dexamethasone treatment. These results showed the effect of O. basilicum and its constituent, rosmarinic acid on inflammatory and oxidant parameters in sensitized rats which was comparable or even more potent than dexamethasone at used concentrations.

Effects of Diet-Induced Obesity on Tracheal Responsiveness to Methacholine, Tracheal Visfatin Level, and Lung Histological Changes in Ovalbumin-Sensitized Female Wistar Rats.

Many studies have shown a close relationship between obesity and asthma severity. In the present study, the effects of diet-induced obesity were examined on airway responsiveness to methacholine in addition to visfatin level in female Wistar rats' tracheae after sensitization with ovalbumin. The rats were divided into four groups: control with normal diet (ND), ovalbumin (OVA)-sensitized with normal diet (S + ND), high-fat diet (HFD), and OVA-sensitized with a high-fat diet (S + HFD). The animals were fed for 8weeks with standard pelts or high-fat diet and then sensitized and challenged with OVA or saline for another 4weeks. At the end of the study, the tracheae were isolated and assessed for airway responsiveness and visfatin protein levels. Diet-induced obesity groups developed increased weight and obesity indices (p < 0.001). After sensitization with OVA and diet-induced obesity, there were marked leftward shifts in methacholine concentration-response curves in S + HFD group compared to other groups. Also, maximum response was the highest (p < 0.05 to p < 0.001), EC50 was the lowest (p < 0.05 to p < 0.001), and visfatin protein level was the highest (p < 0.05 to p < 0.01) in S + HFD. According to results, diet-induced obesity caused airway hyperresponsiveness to methacholine and enhanced visfatin protein levels in the tracheae of ovalbumin-sensitized female rats. Our results suggested that, in obese ovalbumin-sensitized conditions in female rats, the local production of adipocytokines, such as visfatin, may be increased, resulting in the deterioration of inflammation in lungs. This finding shows a possible mechanism for the altered phenotype in obesity-ovalbumin sensitization conditions in female rats.

The Effect of Allium cepa Extract on Lung Oxidant, Antioxidant, and Immunological Biomarkers in Ovalbumin-Sensitized Rats

Objectives: To evaluate the effects of Allium cepa (A. cepa) on levels of oxidants, antioxidants, and immunological markers in bronchoalveolar lavage fluids (BALF) of sensitized rats. Materials and Methods: Oxidant/antioxidant markers and cytokines in BALF of control rats treated with saline (group C), ovalbumin-sensitized rats (group S), rats treated with 1.25 μg/mL dexamethasone and 3 doses of A. cepa extract (35, 70, and 140 mg/kg body weight [BW]/day) (S + AC) were investigated. Comparison of the results between groups was performed using analysis of variance with the Tukey-Kramer post hoc test. Results: The oxidant markers nitrogen dioxide (NO₂), nitrate (NO₃^–), and malondialdehyde (MDA), and immunological markers interleukin (IL)-4 and immunoglobulin E (IgE) were significantly higher, but the antioxidant markers superoxide dismutase (SOD), catalase (CAT), thiol, and interferon (IFN)-γ, and the IFN-γ/IL-4 ratio were lower in sensitized rats compared to control rats (p < 0.001 to p < 0.01). Compared to group S, the levels of the following markers were significantly lower: NO₂, NO₃^–, and IgE in groups treated with the A. cepa extract, MDA and IL-4 levels in groups treated with 70 and 140 mg/kg BW/day of the A. cepa extract, and all these markers as well as IFN-γ in rats treated with dexamethasone (p < 0.001 to p < 0.05). However, there were significantly higher levels of SOD and CAT and an increased IFN-γ/IL-4 ratio (groups treated with 70 and 140 mg/kg BW/day of the A. cepa extract), and levels of thiol and IFN-γ (group treated with 140 mg/kg BW/day of the A. cepa extract) as well as SOD, CAT, and thiol (dexamethasone-treated group) versus group S (p < 0.00 to p < 0.05). Conclusion: A. cepa showed antioxidant and immunomodulatory properties in sensitized rats.