Histopathological Changes Of Nasal Mucosa Research Articles

Konjac-mulberry leaf compound powder alleviates OVA-induced allergic rhinitis in BALB/c mice

According to the proportion of 1:1, konjac flour and mulberry leaf powder are compounded into a kind of dietary fiber source (KMCP). It is found to be good for anti-inflammation. However, its precise anti-allergic rhinitis effect and mechanism remain unknown. In our work, the effect of KMCP on allergic rhinitis (AR) induced by ovalbumin (OVA) was investigated. We found that the number of nasal rubbing and sneezing, the eosinophil (EOS) count in the nasal mucosa, and the serum levels of histamine (HIS), OVA-specific immunoglobulin E (OVA-sIgE) and interleukin-4 (IL-4) were decreased, and the histopathological changes of nasal mucosa were inhibited. Additionally, the experiments further proved that the KMCP treatment could exert substantial effects on short-chain fatty acids (SCFAs) metabolism in the cecum as well. Overall findings suggest that KMCP could suppress the inflammatory response in AR mice, and serve as a novel curative therapeutic for AR without side effects.

Synergistic effect of acupoint injection and moxibustion or catgut embedding or acupuncture on symptoms and expression of Th1/Th2 related cytokines in nasal mucosa of rats with allergic rhinitis

To observe the effect of moxibustion, catgut embedding and acupuncture on allergic symptoms and expression of interferon-γ (IFN-γ) and interleukin-4 (IL-4) of nasal mucosa in rats with allergic rhinitis (AR) based on acupoint injection, so as to explore their synergistic effect and related mechanism in relieving AR. SD rats (half male half female) were randomly divided into normal control, model, acupoint injection (AI), AI+moxibustion, AI+catgut embedding and AI+acupuncture groups, with 8 rats in each group. The AR model was established by intraperitoneal injection of ovalbumin suspension (once every other day for 7 times), and intranasal drop of 0.5% ovalbumin solution (once daily for 7 days). After successful modeling, rats of the AI group received injection of a mixture solution of equal proportion of 1% lidocaine, dexamethasone and transfer factor into "Yingxiang" (LI20) and "Yintang" (EX-HN3) once every 4 days, 4 times altogether. Mild moxibustion or catgut embedment or manual acupuncture was applied to bilateral "Feishu" (BL13) and "Zusanli" (ST36). Both moxibustion (20 min every time) and acupuncture (with the needles retained for 30 min every time) were conducted once daily for 14 times, and catgut embedding was conducted once a week, twice altogether based on acupoint injection. The rats' nasal allergic reaction score (symptom score, 1-3 points) was given according to the times of nose scratching and sneezing, and the running nose state in 30 min, and histopathological changes of nasal mucosa were observed by H.E. staining. The expression levels of IFN-γ and IL-4 in the nasal mucosa were detected by immunohistochemistry and Western blot, separately. Compared with the normal group, the symptom score and the expression of IL-4 positive cells and protein in nasal mucosa were significantly increased (P<0.05), while the expression of IFN-γ positive cells and protein were considerably decreased in the model group (P<0.05). In comparison with the model group, the symptom score and the expression of IL-4 positive cells and protein were obviously decreased (P<0.05), while the expression of IFN-γ positive cells and protein were remarkably increased in the 4 treatment groups (P<0.05). The effects of AI+moxibustion, AI+catgut embedment, AI+acupuncture were signi-ficantly superior to those of simple AI in up-regulating the expression of IFN-γ positive cells and protein and in down-regulating the expression of IL-4 positive cells and protein (P<0.05). Both the symptom score and the expression of IL-4 were notably lower in the AI+moxibustion group than in the AI+catgut embedment and AI+acupuncture groups (P<0.05), whereas the expression of IFN-γ was apparently higher in the AI+moxibustion group than in the other 3 treatment groups (P<0.05). No significant differences were found between the AI+catgut embedment and AI+acupuncture groups in the levels of symptom score, IFN-γ and IL-4 expressions (P>0.05). Moxibustion or catgut embedment or acupuncture and AI have a synergistic effect in relieving symptoms of AR rats, which may be related to their function in regulating the expression levels of nasal IFN-γ and IL-4 proteins. The therapeutic effect of moxibustion is obviously superior to those of both acupuncture and catgut embedment.

Effects of rosmarinic acid on the inflammatory response in allergic rhinitis rat models after PM2.5 exposure.

BackgroundStudies have shown the promising prospects of rosmarinic acid (RosA) for the prevention and treatment of allergic diseases.ObjectiveThe aim of this study was to investigate the effects of RosA on inflammatory reaction in rat models of allergic rhinitis (AR) after PM2.5 exposure.MethodsAllergic rhinitis rat models were established by ovalbumin sensitization, and PM2.5 was applied at a concentration of 1000 μg/m3, 3 h a day for 30 consecutive days. RosA was administered via intraperitoneal injection (20 mg/kg/d) for seven consecutive days. Allergic nasal symptoms were recorded. The expressions of interleukin (IL)‐4, IL‐13, interferon (INF)‐γ, and OVA‐sIgE were determined by ELISA. Histopathological changes in nasal mucosa were observed by HE staining. mRNA expressions of T‐bet and GATA‐3 in nasal mucosa were detected by RT‐PCR. NF‐κBp65 in cell nuclei and IκBα in cytoplasm were analyzed by Western blot.ResultsPM2.5 exposure worsened allergic nasal symptoms in AR rats, while RosA ameliorated these symptoms. Histopathologically, AR rats exhibited disorganized nasal mucosal epithelium, cell exfoliation, eosinophilic infiltration of lamina propria, gland swelling, and submucosal vascular congestion, which were aggravated by PM2.5 exposure and alleviated by RosA. RosA decreased the expressions of IL‐4, IL‐13, and increased the level of IFN‐γ in PM2.5‐exposed AR rats. After RosA intervention, the expressions of GATA‐3 mRNA and NF‐κBp65 in PM2.5‐exposed AR rats were significantly reduced, while those of T‐bet mRNA and IκBα were markedly increased.ConclusionRosmarinic acid may alleviate symptoms of AR rat models exposed to PM2.5 through the modulation of the NF‐κB pathway and Th1/Th2 balance.

Histopathological changes of nasal mucosa after nasal packing with Merocel.

To determine histopathological changes in nasal mucosa associated with duration of nasal packing with Merocel tampons. This study included 24 healthy rabbits, 6 rabbits per group. In group A, no tampon was applied. In group B, Merocel nasal tampons were applied and removed after 24 hours. In group C, the tampons were removed after 48 hours. In group D, the tampons were removed after 5 days. Specimens were obtained from the septum of each rabbit, including cartilage. Histopathological examination was performed. Significant differences were observed in terms of inflammatory infiltration and loss of cilia between groups A and B. Significant differences were also observed in terms of inflammatory infiltration, haematoma, cilia loss, epithelium dysplasia and cartilage degeneration between groups B and C. There were significant differences in terms of cilia loss, epithelium dysplasia and subepithelial fibrosis between groups C and D. Cartilage degeneration was mild in one animal in group B and in two animals in group C, and was moderate in four animals in group C. It is recommended that Merocel nasal tampons are removed within 48 hours to preserve nasal mucosal function. Keeping the pack longer may cause cartilage degeneration and other complications.

Luteolin ameliorates inflammation and Th1/Th2 imbalance via regulating the TLR4/NF-κB pathway in allergic rhinitis rats

Objective Luteolin has an anti-allergic effect but its mechanism is not clear. This study attempted to determine the mechanisms of luteolin in rhinitis. Methods Allergic rhinitis rat model was established by ovalbumin (OVA) stimulation. Then, the rats were treated with normal saline, luteolin, or lipopolysaccharide (LPS) for 14 days. Nasal symptoms were scored; the histopathological changes of nasal mucosa were detected by hematoxylin–eosin staining. Serum levels of Th1 type cytokines (IFN-γ, IL-2), Th2 type cytokines (IL-4, IL-5, IL-13), and OVA-specific IgE (sIgE) were determined by ELISA. The expressions of Toll-like receptor 4 (TLR4) and p65 in nasal mucosa were detected by Western blot or immunohistochemistry. Results Luteolin decreased symptom scores, specifically, the scores in control group, model group, model + 0.1 mg/kg luteolin, model + 1 mg/kg luteolin, and model + 10 mg/kg luteolin groups were 0.63 ± 0.52, 7.88 ± 0.83, 1.38 ± 0.52, 2.75 ± 0.46, and 5.00 ± 0.53, respectively. Luteolin ameliorated nasal mucosa inflammation by promoting the down-regulated levels of Th1 type cytokines, and suppressing the up-regulated levels of Th2 type cytokines, OVE-sIgE, TLR4, and p65. LPS further increased symptom scores, aggravated nasal mucosa inflammation, improved the unbalance of Th1/Th2 type cytokines, and lowered the expressions of OVE-sIgE, TLR4, and p65. Moreover, LPS reversed the effect of luteolin on allergic rhinitis rats. Conclusion Luteolin ameliorated inflammation and Th1/Th2 imbalance via regulating the TLR4/NF-κB pathway in allergic rhinitis rats. This study provided novel evidence that luteolin could be used as a candidate drug in allergic rhinitis treatment.

An integrated approach based on phytochemistry, network pharmacology and metabolomics reveals the mechanism of action of Xanthium strumarium L. for allergic rhinitis.

Xanthium strumarium L. (XS) is a traditional Chinese medicine (TCM) that has been widely used in Chinese medicine prescription for allergic rhinitis (AR). However, the action mechanisms of XS on the therapeutic effects on AR remain elusive. Herein, an integrated approach of phytochemistry, network pharmacology and metabolomics was first applied to uncover the action mechanisms of XS for AR. The therapeutic effect of XS extract on AR was evaluated in rat models of ovalbumin (OVA)-induced AR. The cytokine levels in rat serum and histopathological changes of nasal mucosa were assessed after oral treatment with XS. Chemical compositions of XS were elucidated by phytochemical methods, and active ingredients were identified via ADME-TOX screening in silico. Network pharmacology was performed to establish and analyze the compound-target-disease network so as to find the possible mechanism of XS in treating AR. In addition, metabolomics analysis was applied to investigate the changes in the endogenous metabolite levels that result from XS treatments. As result, the XS extract significantly increased the serum concentrations of IL-2 and reduced the levels of serum IL-4, while XS could ameliorate inflammation in the nasal sub-mucosal area, indicating that XS has significant therapeutic effects on AR model rats. Furthermore, a total of 119 compounds were isolated from XS, and 59 of these compounds were identified as active ingredients through ADME-TOX screening in silico. An in-depth analysis of the network pharmacology implied that the active ingredients of XS could regulate the inflammatory response via “multi-component, multi-target” patterns. In combination with the results of metabolomics, we found that the active ingredients of XS have a beneficial effect on AR through regulating the metabolism of arachidonic acid, which was reflected by medicating the Fc epsilon RI signaling pathway, and the neuroactive ligand–receptor interaction pathway, as well as the key proteins in arachidonic acid metabolism, such as PTGS2, PTGS1, PTGES and ALOX5. Additionally, molecular docking showed that multiple compounds have better binding with PTGS2 and ALOX5, which might be two crucial targets. Overall, these results suggest that the treatment of XS for AR is realized by regulating the metabolism of arachidonic acid via a combination form. This study provides the basis for clinical applications of XS.

Effects of lentivirus-mediated CCR3 RNA interference on the function of mast cells of allergic rhinitis in mice

The CC chemokine receptor 3 (CCR3) expressed by eosinophils, mast cells and Th2 cells is closely related to allergic diseases. The objective of this study was to explore whether silencing of CCR3 with short hairpin RNAs (shRNAs) delivered by a lentiviral vector could impact the function of mast cells in a murine model of allergic rhinitis (AR) in vivo. The murine model of allergic rhinitis (AR) inducing by ovalbumin (OVA) was constructed, and the BALB/c mice were divided into normal control group, AR group, controlshRNA treated group and lentiviral CCR3-shRNA treated group. The recombinant lentivirus vectors which express a short hairpin RNA (shRNA) targeting the CCR3 were dropped into the nasal cavity of OVA-sensitized mice before the challenges. Real-time fluorescence quantitative PCR and western blotting were performed to observe inhibitory effect of CCR3 gene. Nasal symptoms of mice and OVA-specific IgE in each group were assessed. Concentrations of histamine, tryptase and Prostaglandin D2 (PGD2) in bone marrow, peripheral blood and nasal mucosa were analyzed. Furthermore, histological analysis and electron microscopy analysis were applied to detect the histology changes of nasal mucosa and the infiltration of mast cells in nasal mucosa. The results showed that administration of CCR3shRNA could effectively inhibit the expression of the CCR3 gene in bone marrow, peripheral blood and nasal mucosa, which reduced the nasal symptoms, the level of OVA-specific IgE, the inflammatory cells and mast cells infiltration into nasal cavity, and relieved the histopathological changes of nasal mucosa. In addition, intervention of CCR3shRNA could reduce the levels of the histamine, tryptase and PGD2 in bone marrow, peripheral blood and nasal mucosa. These results suggest that inhibition of CCR3 gene expression by shRNAs lentiviral vectors can effectively attenuate migration, infiltration and degranulation of mast cells in local tissues and alleviate the inflammation of allergic rhinitis mice.

The Anti-Allergic Rhinitis Effect of Traditional Chinese Medicine of Shenqi by Regulating Mast Cell Degranulation and Th1/Th2 Cytokine Balance.

Shenqi is a traditional Chinese polyherbal medicine has been widely used for the treatment of allergic rhinitis (AR). The aim of this study was to investigate the anti-allergic rhinitis activity of Shenqi and explore its underlying molecular mechanism. Ovalbumin (OVA)-induced allergic rhinitis rat model was used to evaluate the anti-allergic rhinitis effect of Shenqi. The effect of Shenqi on IgE-mediated degranulation was measured using rat basophilic leukemia (RBL-2H3) cells. Primary spleen lymphocytes were isolated to investigate the anti-allergic mechanism of Shenqi by detecting the expression of transcription factors via Western blot and the level of cytokines (IL-4 and IFN-γ) via ELISA. In OVA-induced AR rat models, Shenqi relieved the allergic rhinitis symptoms, inhibited the histopathological changes of nasal mucosa, and reduced the levels of IL-4 and IgE. The results from the in vitro study certified that Shenqi inhibited mast cell degranulation. Furthermore, the results of GATA3, T-bet, p-STAT6, and SOCS1 expression and production of IFN-γ and IL-4 demonstrated that Shenqi balanced the ratio of Th1/Th2 (IFN-γ/IL-4) in OVA-stimulated spleen lymphocytes. In conclusion, these results suggest that Shenqi exhibits an obvious anti-allergic effect by suppressing the mast cell-mediated allergic response and by improving the imbalance of Th1/Th2 ratio in allergic rhinitis.

Inhibitory Effect of Pycnogenol® on Airway Inflammation in Ovalbumin-Induced Allergic Rhinitis.

The supplement Pycnogenol® (PYC) has been used for the treatment of several chronic diseases including allergic rhinitis (AR). However, the in vivo effects on allergic inflammation have not been identified to date. To investigate the treatment results of PYC on allergic inflammation in a rat model of allergic rhinitis. Animal experimentation. Allergic rhinitis was stimulated in 42 rats by intraperitoneal sensitization and intranasal challenge with Ovalbumin. The animals were divided into six subgroups: healthy controls, AR group, AR group treated with corticosteroid (dexamethasone 1 mg/kg; CS+AR), healthy rats group that were given only PYC of 10 mg/kg (PYC10), AR group treated with PYC of 3mg/kg (PYC3+AR), and AR group treated with PYC of 10 mg/kg (PYC10+AR). Interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10), and OVA-specific immunoglobulin E (Ig-E) levels of serum were measured. Histopathological changes in nasal mucosa and expression of tumor necrosis factor-α (TNF-α) and IL-1β were evaluated. The levels of the IL-4 were significantly decreased in the PYC3+AR, PYC10+AR and CS+AR groups compared with the AR group (p=0.002, p<0.001, p=0.006). The production of the IFN-γ was significantly decreased in the PYC3+AR and PYC10+AR groups compared with the AR group (p=0.013, p=0.001). The administration of PYC to allergic rats suppressed the elevated IL-10 production, especially in the PYC3+AR group (p=0.006). Mucosal edema was significantly decreased respectively after treatment at dose 3 mg/kg and 10 mg/kg PYC (both, p<0.001). The mucosal expression of TNF-α has significantly decreased in the PYC3+AR and PYC10+AR groups (p=0.005, p<0.001), while the IL-1β expression significantly decreased in the CS+AR, PYC3+AR, and PYC10+AR groups (p<0.001, p=0.003, p=0.001). PYC has multiple suppressive effects on allergic response. Thus, PYC may be used as a supplementary agent in allergic response.

Sinupret® oral drops protect against respiratory epithelium atrophy in experimental acute rhinitis

More than 90 % of uncomplicated upper respiratory tract infections are caused by viruses, with a risk of developing subsequent bacterial infections in some patients. The risk of development of microbial complications depends on the degree of viral damage of the structure of the respiratory mucosa and its functions. The objective of this work was to study the effect of Sinupret oral drops on nasal mucosa atrophic changes in a rat model of experimental rhinitis. 60 female rats Wistar were allocated for the experimental study. To study the effect of phytopreparation on atrophy of the nasal epithelium the animals were divided into 3 groups. The 1-st group (n = 20) was without experimental acute rhinitis. The 2-nd group (n = 20) was with experimental acute rhinitis and without treatment with Sinupret®. The 3-rd group (n = 20) with experimental acute rhinitis and treatment with Sinupret®. Experimental rhinitis was induced by placing rats in a swimming pool with cold water, followed by a draught of cool air. The effect of oral Sinupret treatment on histopathological changes in nasal mucosa was assessed on 3 and 14 days post challenge. The results were analyzed using normal or modified Student’s t-test for independent groups. Histological evaluation demonstrated that Sinupret® oral drops applied during acute rhinitis attenuate atrophic and destructive changes of the ciliated epithelium. Oral administration of the herbal medicinal product Sinupret oral drops weakens atrophy of the nasal mucosal ciliated epithelium in a rat model of acute rhinitis.

Anti-inflammatory effect of curcumin on mast cell-mediated allergic responses in ovalbumin-induced allergic rhinitis mouse

Curcumin has commonly been used for the treatment of various allergic diseases. However, its precise anti-allergic rhinitis effect and mechanism remain unknown. In the present study, the effect of curcumin on allergic responses in ovalbumin (OVA)-induced allergic rhinitis mouse was investigated. We explored the effect of curcumin on the release of allergic inflammatory mediators, such as histamine, OVA-specific IgE, and inflammatory cytokines. Also, we found that curcumin improved rhinitis symptoms, inhibited the histopathological changes of nasal mucosa, and decreased the serum levels of histamine, OVA-specific IgE and TNF-α in OVA-induced allergic rhinitis mice. In addition, curcumin suppressed the production of inflammatory cytokines, such as TNF-α, IL-1β, IL-6 and IL-8. Moreover, curcumin significantly inhibited PMA-induced p-ERK, p-p38, p-JNK, p-Iκ-Bα and NF-κB. These findings suggest that curcumin has an anti-allergic effect through modulating mast cell-mediated allergic responses in allergic rhinitis, at least partly by inhibiting MAPK/NF-κB pathway.

방풍(防風)의 난알부민 유도 알레르기 비염 마우스에서의 항알레르기 효능 연구

Objectives : In this study, we investigated the effect of Saposhnikoviae Radix on allergic responses in ovalbumin(OVA)-induced Allergic rhinitis(AR) mice. Methods : BALB/c mice were orally administrated with Saposhnikoviae Radix water extract (SRW, 50 mg/kg) or anti-histamine drug, Ketotifen (10 mg/kg) as a reference drug, followed by sensitization and challenge of OVA. Mice were measured clinical symptoms and the serum levels of histamine, IgE, IL-4, and IFN-<TEX>${\gamma}$</TEX>, and observed histopathological changes of nasal mucosa H&E staining. Results : SRW significantly decreased rubs and the serum levels of histamine, IgE, and IL-4, and then increased the serum levels of IFN-<TEX>${\gamma}$</TEX> in OVA-induced AR mice, and inhibited histopathological changes of nasal mucosa with inflammation and the eosinophils infilteration. Conclusions : These data suggest that SRW has anti-allergic effect through the inhibitory property of Saposhnikoviae Radix against allergic responses in allergic rhinitis.

알레르기 비염 한약제제 KOB와 주요 구성약물인 황기(黃芪)의 난알부민 유도 알레르기 비염 마우스에서의 항알레르기 효능 연구

Objectives : In this study, we investigated the effect of KOB, a polyherbal medicine for allergic rhinitis and its main herb, Astragali Radix on allergic responses in ovalbumin (OVA)-induced Allergic rhinitis(AR) mice. Methods : Sprague Dawley (SD)-rats were orally administrated with KOB (500 mg/kg), Astragali Radix water extract (ARW, 100 mg/kg) or anti-histamine drug, dosodium cromoglycate (50 mg/kg) as a reference drug, and then intraperitoneally injected with compound 48/80 (8 mg/kg). Rats were measured the mortality and serum levels of histamine. BALB/c mice were orally administrated with KOB (500 mg/kg), ARW (100 mg/kg) or anti-histamine drug, Ketotifen (10 mg/kg) as a reference drug, followed by sensitization and challenge of OVA. Mice were measured the serum levels of histamine and IgE, and observed histopathological changes of nasa mucosa H&E staining. Results : KOB and ARW significantly decreased the mortality and the serum levels of histamine in compound 48/80-induced anaphylatic rats. KOB and ARW also decreased the serum levels of histamine and IgE in OVA-induced AR mice, and inhibited histopathological changes of nasal mucosa with inflammation and the eosinophils infilteration. Conclusions : These data suggest that KOB has a strong anti-allergic effect through the inhibitory property of Astragali Radix, the main component of KOB against allergic responses in allergic rhinitis.

Antiallergic effect of KOB03, a polyherbal medicine, on mast cell-mediated allergic responses in ovalbumin-induced allergic rhinitis mouse and human mast cells

Ethnopharmacological relevanceKOB03 is a polyherbal medicine consisting of five different herbs and has commonly been used for the treatment of various allergic diseases. However, its precise anti-allergic effect and mechanism remain unknown. Aim of the studyThe aim of this study was to investigate the effect of KOB03 on allergic responses through the regulation of mast-cell mediated allergic inflammation. Materials and methodsTo determine the effect of KOB03 on mast cell-mediated allergic reactions, we investigated the parameter changes of in vivo models such as compound 48/80-induced systemic anaphylaxis and ovalbumin (OVA)-induced allergic rhinitis, and the release of allergic inflammatory mediators such as histamine, immunoglobulin (Ig) E, and inflammatory cytokines via the MAPKs and NF-kappaB pathways. ResultsThe oral administration of KOB03 at doses of 100 and 200mg/kg inhibited histamine release and mortality in compound 48/80-induced anaphylactic rats. KOB03 also improved rhinitis symptoms, inhibited the histopathological changes of nasal mucosa, and decreased the serum levels of histamine, OVA-specific IgE and TNF-α in OVA-induced allergic rhinitis in mice. In vitro, KOB03 suppressed compound 48/80-induced histamine release by blocking mast cell degranulation. In addition, KOB03 inhibited the production of inflammatory cytokines such as TNF-α, IL-1β, IL-6 and IL-8 in PMA/A23187-stimulated HMC-1 mast cells by suppressing their gene expression and blocking the ERK1/2 and p38 MAPK and NF-κB pathways. ConclusionsThese results suggest that KOB03 has an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis.

Effects of KOB03, a polyherbal medicine in mast cell-mediated allergic response in ovalbumin-induced allergic rhinitis in vivo model and RBL-2H3 mast cells. (177.14)

Abstract KOB03 is a polyherbal medicine originating from Korean Traditional Medicine, which has been clinically applied for the treatment of allergic diseases. Here, we investigated the inhibitory effects of KOB03 on mast cell-mediated allergic responses on ovalbumin-induced allergic rhinitis in guinea pigs and RBL-2H3 mast cells. To determine the effect of KOB03 on mast cell-mediated allergic reactions, we investigated the parameter changes on ovalbumin (OVA)-induced allergic rhinitis in guinea pigs, and the release of allergic inflammatory mediators such as histamine, IgE and inflammatory cytokines in DNP-IgE-stimulated RBL-2H3 mast cells. The oral administration of KOB03 at doses of 200 and 500 mg/kg in OVA-sensitized/challenged guinea pig significantly decreased the serum levels of OVA-specific IgE, histamineand TNF-alpha KOB03 also inhibited the histopathological changes of nasal mucosa with the infilteration of eosinophils and inflammatory cells. Furthermore, KOB03 significantly inhibited DNP-IgE-induced release of histamine in RBL-2H3 cells via suppressing the ERK1/2 phosphorylation. These data suggest that KOB03 has an anti-allergic activity by modulating mast cell-mediated allergic responses.

Effect of early allergen immunization on the development of allergic rhinitis in mouse

To investigate the effect of early allergen exposure on later development of allergic rhinitis in mouse. Twenty-four BALB/c neonates were randomly divided into 4 groups (low-dose group, high-dose group, negative control group and positive control group), each group had 6 mice. The mice were administered ovalbumin (OVA) by subcutaneous injection on day 1, 5, 12 after birth (10 μg OVA in 0.05 ml saline for low-dose group, 1000 μg OVA in 0.05 ml saline for high-dose group, only saline for negative and positive control group). Then the mice were sensitized and intranasally challenged with OVA (saline without OVA was used in negative control group) after 6 weeks. Symptoms, histopathological changes of nasal mucosa were observed, OVA-IgE in serum was examined, cytokines IL-4, IL-5 and IFN-gamma were detected in the supernatant of cultured splenic mononuclear cells. Compared to the positive control group, symptoms and nasal mucosa histological changes of high-dose group was indistinctive. The level of OVA-IgE and cytokines IL-4, IL-5 (x(-) +/- s) in high-dose group [(265.11 +/- 26.29), (446.39 +/- 72.83) and (171.24 +/- 15.66) pg/ml, respectively] were significantly lower than those in positive control group [(665.85 +/- 43.15), (1113.45 +/- 30.47), (255.36 +/- 30.96) pg/ml, respectively, t value were 0.000, 0.000 and 0.009, respectively, all P < 0.05]. The level of IFN-γ in high-dose group [(319.74 +/- 56.30) pg/ml] was significantly higher than those in positive control group [(170.02 +/- 14.50) pg/ml, t = 0.000, P < 0.05]. There was no significant difference of the results between the low-dose group and positive control group. Neonatal immunization with high-dose OVA inhibited the future allergic rhinitis symptoms, nasal histological changes, serum OVA-IgE levels and Th1/Th2 cytokine imbalance, resulting in the protective effect.

Effects of Minimal Persistent Inflammation on Nasal Mucosa of Experimental Allergic Rhinitis

Minimal persistent inflammation (MPI) is considered another piece of the complex puzzle of allergic inflammation. Although some studies regarding MPI have been reported, no study has evaluated the effects of MPI on the structure changes at the site of allergic reaction. This study investigates whether long-time MPI during allergic rhinitis (AR) results in some features of tissue remodeling in the nasal mucosa. An animal model of MPI was developed by repeated nasal challenge with low concentration of ovalbumin (OVA) in sensitized guinea pigs. The models were assessed by allergic symptom after antigen challenge, eosinophil infiltration in the nasal mucosa, and intercellular adhesion molecule (ICAM) 1 expression on nasal epithelial cells. The histopathological changes in nasal mucosa were determined by Alcian blue-periodic acid-Schiff and Masson's trichrome staining. The expression of transforming growth factor (TGF) beta(1) and matrix metalloproteinase (MMP) 9 was examined by immunofluorescence under a confocal laser scan microscope. When sensitized animals were challenged with the low concentration of 0.01% OVA, the symptom of sneezing disappeared, but there were still mild eosinophils infiltration and weak ICAM-1 expression, which indicated the success of MPI models. Moreover, the number of goblet cells and the percentage area of collagen deposition were both mildly increased. The expression of MMP-9 and TGF-beta(1) was also weakly elevated. We have successfully established MPI models and proved long-time MPI may result in mild features of remodeling in the nasal mucosa, which provide new insights into the unexpected potential effects of MPI on the structural changes.

Histopathological changes of rat larynx mucosa with exposure to chronic thinner inhalation

Objective Histopathological changes in nasal mucosa, trachea, and pulmonary system with exposure to chronic thinner inhalation have been studied in the literature. However, the possible changes in larynx mucosa, which is a part of the upper airway tract, have not been studied yet. The aim of this study is to determine the histopathological changes of rat larynx mucosa with exposure to chronic thinner inhalation. Study Design and Setting Randomized trial. The study was conducted at the animal care facility of Haydarpasa Numune Education and Research Hospital. Subjects and Methods Fifty-one Sprague-Dawley rats were used throughout the experiment. Four groups of rats inhaled thinner in a glass cage for 2, 4, 8, and 12 weeks respectively. Seven rats inhaled only the air in the room as the control group. Results The comparison of inflammation and exocytosis in the control and 2 week groups revealed no significant difference ( P > 0.05), but from the beginning of 4 weeks of thinner inhalation, statistically significant differences were observed ( P < 0.05). From the beginning of 8 weeks of thinner inhalation, statistically significant differences were observed in larynx mucosa when we assessed metaplasia and cilia loss distribution among groups ( P < 0.05). Conclusion On the basis of histopathological evaluations, it was shown that the harmful effect of inhalation of thinner in high concentrations to larynx mucosa is similar to the effect on other organs of the respiratory system.

The effect of benzalkonium chloride on rabbit nasal mucosa in vivo: an electron microscopy study.

In this study we investigated the histopathological changes of nasal mucosa after the use of topical benzalkonium-chloride solution. In the study, 28 male New Zealand white rabbits were used. The animals were divided into two groups. In the first group, 50 micro l of 0.001% benzalkonium-chloride solution was sprayed into the right nostril and 50 micro l of 0.9% saline into the left twice daily for 14 days. In the second group, the same solutions were applied twice daily for 28 days. All of the biopsies from each nasal cavity were processed for electron microscopy. In the nostrils treated with 0.001% benzalkonium chloride, there were areas with obvious squamous cell metaplasia. Some cells showed broken cristae of the mitochondria. Degenerative changes in the supportive and olfactory cells, deformation of nuclei and the increase of heterochromatin were observed. The present investigation has shown that the application of topical benzalkonium chloride does induce degenerative morphologic changes in the nasal mucosa in rabbits in vivo.

Histopathological Changes in Nasal Mucosa of Workers at a Norwegian Nickel Refinery

Histopathological Changes in Nasal Mucosa of Workers at a Norwegian Nickel Refinery