Efficacy of parthenolide on lung histopathology in a murine model of asthma.

BACKGROUND: Parthenolide is the active constituent of the plant 'Tanacetum parthenium' (Feverfew) which has been used for centuries as a folk remedy for inflammatory conditions. AIM OF THE STUDY: In this study we aimed to investigate the effects of parthenolide in a murine model of chronic asthma. MATERIALS AND METHODS: Thirty-five BALB/c mice were divided into five groups; I (control), II (placebo), III (dexamethasone), IV (parthenolide) and V (dexamethasone and parthenolide combination). Lung histology was evaluated after treatment with the study drugs. Levels of interleukin (IL)-4 and IL-5 were determined by ELISA. RESULTS: Histologic parameters except the number of mast and goblet cells improved in the parthenolide group when compared with placebo. All parameters except basal membrane thickness and number of mast cells were improved significantly better in the group receiving dexamethasone when compared with the parthenolide group. Improvement of most of the histologic parameters was similar in Groups III and V. Interleukin-4 levels were significantly reduced in the parthenolide group when compared to the placebo group. CONCLUSION: We demonstrated that parthenolide administration alleviated some of the pathological changes in asthma. But parthenolide alone is not efficient as dexamethasone therapy and the parthenolide and dexamethasone combination also did not add any beneficial effect to the dexamethasone treatment.

Beneficial effects of arginase inhibition and inhaled L-arginine administration on airway histology in a murine model of chronic asthma.

BACKGROUND: Increased arginase activity in the airways induces reduced bioavailability of L-arginine and cause deficiency of bronchodilatating and anti-inflammatory nitric oxide (NO). Therefore, arginine and arginase inhibitors may have therapeutic potential in the treatment of asthma. Using a murine model of asthma, we aimed to investigate the effects of inhaled L-arginine and arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA) and co-treatment on airway histology of asthmatic lung tissue. METHODS: Forty-two BALB/c mice were divided into six groups: I (control), II (placebo), III, IV, V and VI. All mice except for control group were sensitised by an intraperitoneal injection of ovalbumin with alum adjuvant and then challenged with an aerosol of ovalbumin on three days of the week for eight weeks beginning from the 21st day of the study. Lung histology and bronchoalveolar lavage cell (BAL) counts were evaluated after treatment with inhaled L-arginine, nor-NOHA, l-arginine-nor-NOHA combination, budesonide and placebo. Interleukin(IL)-4 and IL-5 levels are determined in lung homogenates with ELISA. RESULTS: L-Arginine group was similar to budesonide group in lowering all histological parameters. Results of groups treated with nor-NOHA were also similar to budesonide group except for epithelial thickness. The number of eosinophils in BAL decreased significantly in groups receiving study drugs. Decrease was only noted in IL-4 levels in group receiving nor-NOHA. CONCLUSION: We demonstrated that inhaled l-arginine administration alleviated all histological parameters similar to budesonide and treatment with arginase inhibitor improved not all but some of the pathological changes in chronic asthma. Combination therapy had no additive effect on either treatment.

Beneficial effects of erythropoietin on airway histology in a murine model of chronic asthma.

BACKGROUND: Erythropoietin (EPO) is originally defined as a haematopoietic growth factor, but also has anti-inflammatory effects through cytokine modulation. This anti-inflammatory and cytokine modulating effect has not been investigated for the treatment of asthma. We aimed to determine the beneficial effects of erythropoietin on lung histology of murine model of chronic asthma. METHODS: Thirty-five BALB/c mice were divided into five groups: I; II; III; IV; and control group. All groups except control group were sensitised and challenged with ovalbumin. Mice with experimentally induced asthma in Group I received saline; Group II EPO 500IU/kg; Group III EPO 1000IU/kg; and Group IV dexamethasone 1mg/kg intraperitoneally once a day in the last five days of the challenge period. Animals were sacrificed 24h after the last administration of study drugs. Histological findings of airways were evaluated by light and electron microscopic examination. RESULTS: All histological parameters of asthma in the group treated with a high dose of EPO (Group III) were significantly ameliorated when compared with the group treated with saline (Group I). In comparison to the group treated with low dose of EPO (Group II) and the group treated with saline (Group I), basement membrane thicknesses and number of mast cells were significantly lower in the group treated with low dose of EPO (Group II). All histological parameters were similar between the group treated with high dose of EPO (Group III) and the group treated with dexamethasone (Group IV) except higher number of mast cells in the group treated with high dose of EPO (Group III). Additionally, the results of all histological parameters in the group treated with high dose of EPO (Group III) were significantly better when compared with the group treated with low dose of EPO (Group II). CONCLUSIONS: We found that EPO ameliorated histological changes of chronic murine model of asthma. Further studies are needed to evaluate the efficacy of EPO in the treatment of asthma.

Histopathologic changes in two mouse models of asthma.

BACKGROUND: No studies to date have compared mouse models of asthma by evaluating airway histopathology. OBJECTIVE: To compare 2 such models by studying chronic histopathologic changes of the airways using light and electron microscopy. METHODS: Twenty-one male BALB/c mice were divided into 3 groups: a nebulization group sensitized via an intraperitoneal injection of 10 microg ovalbumin on days 0 and 14 and exposed to 2.5% aerosolized ovalbumin 3 days a week over the subsequent 8 weeks; an intranasal group sensitized via 2 intraperitoneal injections of 100 microg ovalbumin on days 0 and 14 and administered an intranasal dose of 500 microg ovalbumin on days 14, 27, 28, 29, 47, 61, 73, 74, and 75; and a control group that received nothing. Airway histopathologies were evaluated. RESULTS: Basement membrane, epithelium, and subepithelial smooth muscle layer thicknesses and mast and goblet cell numbers were significantly higher in the nebulization group than in the control group. With the exception of mast cell numbers, these parameters were also significantly higher in the intranasal group than in the control group. On comparing the intranasal and the nebulization group, goblet cell numbers were significantly higher in the former and mast cells in the latter. CONCLUSION: Both models replicated all the structural parameters of asthma except for mast cell numbers in the intranasal group (no significant difference with respect to the control group). Our findings do not provide sufficient evidence that one protocol is superior to the other. Larger studies are needed to compare different asthma protocols.

Effectiveness of thymoquinone in the treatment of experimental asthma.

BACKGROUND: Thymoquinone (TQ), the main active constituent of the volatile oil extracted from Nigella sativa's seeds, is used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects. METHODS: Twenty-eight BALB/c female mice were divided into four groups: I (sham-operated control group), II, III, and IV. All groups except for the sham-operated group were sensitized and challenged with ovalbumin. The sham-operated group received nebulized saline in challenge period. Mice in groups III and IV were administered TQ at a dose of 3 mg/kg and dexamethasone 1 mg/kg, respectively, intraperitoneally once a day for the final 5 days of the challenge period. Animals were sacrificed 24 h after the last drug administration and the airway samples were evaluated histologically by light microscopy. RESULTS: All histological parameters in Group III, similar to Group IV, were improved when compared to Group II. All variables except numbers of goblet cells were found to be significantly better in Group III and Group IV compared to Group II. CONCLUSIONS: In our study, we demonstrated that TQ administration alleviates the pathological changes of chronic asthma. TQ might be a promising therapy for asthma in the.