Rosmarinic acid affects immunological and inflammatory mediator levels and restores lung pathological features in asthmatic rats.

BACKGROUND: The effects of rosmarinic acid (RA) on immunological and inflammatory mediator levels in bronchoalveolar lavage fluid (BALF) as well as lung pathological changes in asthmatic rats were investigated. METHODS: The levels of IFN-γ, IL-4, IFN-γ/IL-4 ratio, IgE, PLA2, and total protein (TP) in BALF and pathological changes in the lung were evaluated in control group (C), asthma group (sensitized to ovalbumin) (A), asthma groups treated with RA and dexamethasone. RESULTS: Compared to the control group, asthmatic rats showed increased levels of IL-4, IgE, PLA2, and TP as well as all pathological scores with decreased levels of IFN-γ and IFN-γ/IL-4 ratio (P<0.05 to P<0.001). The levels of IL-4, IgE, PLA2, and TP significantly reduced in groups treated with all concentrations of RA compared to asthma group (P<0.001 for all cases). IFN-γ was significantly decreased in groups treated with two lower concentrations of RA but IFN-γ/IL-4 ratio was increased in groups treated with two higher concentrations of RA compared to asthma group (P<0.05 to P<0.001). Treatment with all doses of RA led to significant improvement in pathological scores in asthmatic animals (P<0.05 to P<0.001). Most measured parameters were also significantly improved in dexamethasone-treated animals (P<0.01 to P<0.001) but IFN-γ/IL-4 ratio and the scores of interstitial fibrosis, bleeding and epithelial damage did not change in this group. CONCLUSION: The results indicated a preventive effect for RA on immunological and inflammatory mediators as well as lung pathological changes in asthmatic rats which were comparable or even more potent than that of dexamethasone.

Carvacrol ameliorates haematological parameters, oxidant/antioxidant biomarkers and pulmonary function tests in patients with sulphur mustard-induced lung disorders: A randomized double-blind clinical trial.

WHAT IS KNOWN AND OBJECTIVE: In this study, the effect of carvacrol (CAR) on pulmonary function tests (PFT), haematological indices and oxidant/antioxidant biomarkers in patients with sulphur mustard (SM)-induced lung disorders was examined. METHODS: Twenty patients exposed to SM 27-30 years ago were divided into two groups and treated with either placebo (P) or CAR (1.2 mg/kg per day) (n = 10 for each group). Forced vital capacity (FVC), peak expiratory flow (PEF), total and different white blood cell (WBC), haematological parameters and oxidant/antioxidant biomarkers were measured at the baseline (step 0), one and two months (steps I and II, respectively) after starting the treatment. RESULTS AND DISCUSSION: PEF was significantly increased in the CAR-treated group in step II compared to step 0 (P < .01). Total WBC (P < .01) and neutrophil (P < .05) count in the CAR-treated group were significantly decreased in the group in steps I and II (P < .01 for both cases) compared to step 0. The levels of thiol, superoxide dismutase and catalase in the CAR-treated group were significantly increased (P < .05 to P < .001) in steps I and II, but malondialdehyde significantly decreased in step II compared to step 0 (P < .01). The percentage of total and differential WBC, oxidant/antioxidant biomarkers, FVC and PEF values following a two-month treatment period were significantly improved in the CAR-treated group compared to the placebo group (P < .05 to P < .001). WHAT IS NEW AND CONCLUSION: Two-month treatment with CAR reduced inflammatory cells and oxidant biomarkers, whereas increased antioxidant biomarkers and improved PFT tests in SM-exposed patients.

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.

The impact of "Ramadan fasting period" on total and differential white blood cells, haematological indices, inflammatory biomarker, respiratory symptoms and pulmonary function tests of healthy and asthmatic patients.

BACKGROUND: There is no conclusive evidence regarding the effect of fasting on different features in asthmatic patients. In the present study, the effect of Ramadan fasting in asthmatic patients and healthy control was studied. METHODS: Haematological indices, inflammatory mediators, pulmonary function tests (PFT) and respiratory symptoms were evaluated in 15 asthmatic patients compared to 14 healthy matched control group before and after the one-month fasting period in Ramadan. The change in each parameter from the beginning to the end of Ramadan was calculated and referred to as "variation during Ramadan". RESULTS: The values of MCH, MCHC in both groups and monocyte counts in asthmatic patients, were significantly increased but platelet count was reduced in asthmatic and controls respectively compared to pre-Ramadan fasting period (P<0.05 to 0.001). Serum hs-CRP level in control and asthmatic groups was significantly reduced after Ramadan fasting month (P<0.001 for both groups). PFT values after Ramadan fasting month in both groups were non-significantly higher compared to pre-fasting values except FVC. Respiratory symptoms in asthmatic patients were non-significantly but wheeze-o was significantly reduced after Ramadan fasting period in asthma group (P<0.05). There was no significant difference in variations of different parameters during Ramadan fasting period between two groups, although reduction of hs-CRP in asthmatic group was non-significantly higher than control group. CONCLUSION: These results show that Ramadan fasting period has no negative impact on asthma and may have some positive effect on asthma severity with regard to reduction of hs-CRP concentration and chest wheeze.

The Effect of Zataria multiflora and its Constituent, Carvacrol, on Tracheal Responsiveness and Lung Pathology in Guinea Pig Model of COPD.

The effects of Zataria multiflora (Z. multiflora) and its constituent, carvacrol, in guinea pigs model of chronic obstructive pulmonary disease (COPD) were examined. Animals were divided into control, COPD, COPD + drinking water containing three concentrations of extract of Z. multiflora (0.4, 0.8 and 1.6 mg/ml), COPD + drinking water containing three concentrations of carvacrol (60, 120 and 240 µg/ml) and COPD + dexamethasone (50 µg/ml). COPD was induced by exposing animals to cigarette smoke for 3 months. Emphysema as a pathological change of the lung and tracheal responsiveness were measured (n = 5 for control and COPD groups and n = 6 for another groups). Tracheal responsiveness (p < 0.05) and emphysema were significantly increased (p < 0.001) in COPD compared to the control group. Tracheal responsiveness in COPD groups treated with two higher concentrations of the Z. multiflora and three concentrations of carvacrol, and emphysema in treated with highest concentration of Z. multiflora and carvacrol were significantly improved compared to COPD group. Studied parameters were also significantly improved in the treated group with dexamethasone compared to COPD animals (p < 0.05 to p < 0.01). The results indicated a preventive effect of Z. multiflora extract and its constituent, carvacrol, on tracheal responsiveness and pathological changes of the lung.

The effect of exposure to chlorine on pulmonary function tests and respiratory and allergic symptoms in Iranian lifeguards.

Lifeguards are frequently exposed to various irritant chemicals including chlorine during work, which can induce respiratory and allergic disorders. In this study, pulmonary function tests (PFTs) and self-reported respiratory and allergic symptoms in lifeguards were compared with matched control subjects. The frequency of respiratory and allergic symptoms was evaluated in a sample of 38 Iranian male lifeguards and 38 control subjects with similar age, having other jobs from the general population, using a questionnaire including questions on work-related respiratory and allergic symptoms in the past year, smoking habits, and duration of working as a lifeguard. PFTs were also measured in lifeguard subjects before and 15 min after 200 µg inhaled salbutamol and baseline PFT in controls. A total of 22 (55%) participants reported work-related respiratory symptoms. Sputum (39.4%) and cough (18.4%) were the most common symptoms and only 7.9% and 15.8% of lifeguards reported wheezing and shortness of breath, respectively. Both sputum and breathlessness were significantly higher in lifeguards than control group (p < 0.05 and p < 0.005, respectively). Most allergic symptoms (sneezing and runny nose) in lifeguards were also significantly greater than control group (p < 0.05 for both cases). In addition, all respiratory (except sputum and wheezing) and allergic symptoms were significantly higher in lifeguards during work compared with rest period (p < 0.05 to p < 0.005). Most PFT values were also significantly lower in lifeguards than control subjects (p < 0.05 to p < 0.001). In addition, most (all) PFT values were significantly improved after 200 µg inhaled salbutamol (p < 0.05 to p < 0.001). These results showed that lifeguards have higher frequencies of work related respiratory symptoms and allergic symptoms particularly during the work period. PFT values were also significantly reduced among lifeguards.

The effect of lead exposure on tracheal responsiveness to methacholine and ovalbumin, total and differential white blood cells count, and serum levels of immunoglobulin E, histamine, and cytokines in guinea pigs.

The effect of exposure to inhaled lead acetate in guinea pigs was evaluated. The present study comprised of five groups of guinea pigs including control (C), sensitized to ovalbumin (OA; S) and three groups exposed to 0.1, 0.2, and 0.4 M inhaled lead (Pb; n = 6 for each group). Tracheal responsiveness to methacholine and OA, total and differential white blood cells (WBCs) count in lung lavage, serum levels of cytokines (interferon γ (IFN-γ) and interleukin 4 (IL-4)), histamines, and immunoglobulin E (IgE), and Pb concentration in lung were measured. Tracheal responsiveness to methacholine, OA, total and differential WBC types as well as IL-4, IFN-γ, histamine, and IgE were significantly increased but IFN-γ/IL-4 were significantly decreased in sensitized animals as well as those exposed to high Pb concentrations when compared with the control group (from p < 0.05 to p < 0.001). In addition, there was not a significant difference in most measured values between animals exposed to high Pb concentration and group S. The Pb concentration in lung tissues of animals exposed to all three Pb concentrations was significantly higher than that of group C (p < 0.001 for all cases).These results showed that inhaled lead acetate exposure can induce lung inflammatory changes similar to sensitized animals. Therefore, exposure to environmental Pb pollution may cause asthma-like changes.

The Effect of Hydroethanol Extract of Achillea Millefolium on ß-adrenoceptors of Guinea Pig Tracheal Smooth Muscle.

Different pharmacological effects of Achillea millefolium including its relaxant effect on smooth muscle have been shown previously. In the present study the stimulatory effect of the plant extract on ß-adrenoceptor of tracheal muscle was examined in order to investigate one possible mechanism for its observed relaxant effect. Effect of three concentrations of hydroethanol extract, 10 nM propranolol, and saline on ß-adrenoceptor was tested in two experimental groups including; nonincubated tracheal smooth muscles (group 1) and incubated tracheal smooth muscle with chlorpheniramine (group 2). Concentration response curves to isoprenaline were performed in precontracted tracheal smooth muscle in the presence of the extract, propranolol and saline. Values of EC50 and CR-1 were measured. Leftward shifts in isoprenaline curves were observed in the presence of medium and high concentrations of the extract compared with saline in both groups. The values of EC50 obtained in the presence of medium and high concentrations of the extract only in group 1 were nonsignificantly lower than that of saline. The values of CR-1 obtained in the presence of all concentrations of the extract in both groups were negative and significantly different with that of propranolol. The results indicated a small stimulatory effect of the extract on ß2-adrenoceptors.

The potential effect of the extract of Crocus sativus and safranal on the total and differential white blood cells of ovalbumin-sensitized guinea pigs.

Previous studies have indicated relaxant, inhibitory effect on histamine (H1) and muscarinic receptors, and stimulatory effect on ß-drenoceptor of Crocus sativus on guinea pig tracheal chains. In the present study, the effect of the extract of C. sativus and one of its constituents, safranal, on the inflammatory changes of sensitized guinea pigs was examined. Eight groups of sensitized guinea pigs to ovalbumin were studied. One group was given drinking water alone (group S), while other 7 groups were received drinking water containing; three concentrations of safranal (4, 8 and 16 µg/ml), three concentrations of extract (0.1, 0.2 and 0.4 mg/ml) and one concentration of dexamethasone (S+D group), (six animal in each group). Total and differential white blood cell (WBC) counts in blood were evaluated. Total blood WBC number, eosinophyl and lymphocyte percentage in blood were increased, but neutrophil decreased in sensitized animals compared to those of control groups (P<0.05 to P<0.001). Treatment of animals with dexamethasone, all concentrations of the extract and safranal significantly improved most types of WBCs but total WBC number was only decreased in treated groups with dexamethasone and high concentration of the extract compared to group S (P<0.05 to P<0.001). Safranal was more effective in the improvement of eosinophil and lymphocyte compared to the extracts (P<0.001 for both cases). However, the preventive effect of the extract of C. sativus on total WBC count was more prominent than that of the safranal (P<0.01). These results showed a preventive effect of the extract of C. sativus and its constituent safranal on total and differential count of WBC in blood of sensitized guinea pigs. The results also suggest that the effect of the plant is perhaps due to its constituent of safranal.

The effect of the extract of Crocus sativus and its constituent safranal, on lung pathology and lung inflammation of ovalbumin sensitized guinea-pigs.

Different pharmacological effects of Crocus sativus have been demonstrated on guinea pig tracheal chains in previous studies. In the present study, the prophylactic effect of the extract of C. sativus and its constituent, safranal on lung pathology and total and differential white blood cells (WBC) of sensitized guinea pigs was examined. Guinea pigs were sensitized with injection and inhalation of ovalbumin (OA). One group of sensitized guinea pigs were given drinking water alone (group S) and three groups were given drinking water containing three concentrations of safranal (S+SA1, S+SA2 and S+SA3 groups), three groups, drinking water containing three concentrations of extract (S+CS1, S+CS2 and S+CS3 groups) and one group drinking water containing one concentration of dexamethasone (S+D group) (n=6, for all groups). The lung pathology was evaluated in control, non treated and treated sensitized groups. Total and differential WBC counts of lung lavage were also examined. All pathological indices in group S showed significant increased compared to control group (p<0.05 for lung congestion and p<0.001 for other groups). Total WBC number (p<0.001), eosinophyl percentage (p<0.001) in lung lavage and serum histamine levels (p<0.01) were also increased in sensitized animals compared to those of controls. Treatment of S animals with dexamethasone, all concentrations of the extract and safranal significantly improved lung pathological changes, most types of WBC and serum histamine levels compared to group S (p<0.05-0.001). Treatment of S group with first concentration of safranal also decreased total WBC. Treatment with safranal was more effective in improvement of most pathological changes, total and differential WBC count as well as serum histamine level (p<0.05-0.001). These results showed a preventive effect of the extract of C. sativus and its constituent safranal on lung inflammation of sensitized guinea pigs. The results also showed that the effect of the plant is perhaps due to its constituent safranal.

Pulmonary function tests and respiratory symptoms among smokers in the city of Mashhad (north east of Iran).

The prevalence of smoking was studied using a questionnaire. Pulmonary function tests and respiratory symptoms were evaluated in 176 smokers. The total studied population with family and co-workers were 13289. The number of smokers among studied population was 11.7%. The rate of smoking among male subjects was 17.2% and in female 2.5%. All values of PFTs in smokers were significantly lower (p<0.001) and respiratory symptoms higher than in non smokers (p<0.05 for cough and p<0.001 for wheeze and tightness). There were significant negative correlations between smoking duration and rate with values of PFT (p<0.05-p<0.001). In this study the prevalence of smoking in population of Mashhad city was shown. The prevalence of smoking was higher among male than females. Smoking leads to increased respiratory symptoms and reduction of PFTs values.

The effect of carvacrol on muscarinic receptors of guinea-pig tracheal chains.

The effects of three concentrations of carvacrol, the constituent of Zataria multiflora Boiss (a monoterpenoid phenol, C(10) H(14) O) and 10 nm atropine on muscarinic receptors were tested on: non-incubated (n = 7), incubated tracheal chains with propranolol and chlorpheniramine (n = 6) and incubated with propranolol (n = 5). The EC(50) of all three concentrations of carvacrol in incubated tissues with propranolol and chlorpheniramine was significantly greater than those of incubated tissues with propranolol and non-incubated trachea (p < 0.05 to p < 0.001). The EC(50) of two higher concentrations of carvacrol (0.2 and 0.4 µg/mL) in incubated tissues with propranolol was also significantly greater than those of non-incubated trachea (p < 0.01 to p < 0.001). The maximum response in the presence of all concentrations of carvacrol in non-incubated and incubated tissues with propranolol and chlorpheniramine and those of its two higher concentrations (0.2 and 0.4 µg/mL) in incubated tissues with propranolol were lower than saline (p < 0.05 to p < 0.001). There were parallel rightward shifts in the concentration-response curves in the presence of all concentrations of carvacrol in non-incubated and incubated tissues with propranolol and its lower concentration in incubated tissues with propranolol and chlorpheniramine. These results indicated an inhibitory effect of carvacrol on muscarinic receptors. A ß-adrenoceptor stimulatory effect was also suggested for carvacrol.

Inhibitory effect of Crocus sativus (saffron) on histamine (H1) receptors of guinea pig tracheal chains.

The inhibitory effects of aqueous-ethanolic extracts of Crocus sativus (Iridaceae), on histamine (H1) receptors was examined on tracheal chains of guinea pigs. The effects of three concentrations of aqueous-ethanolic extract, 10 nM chlorpheniramine, and saline on histamine (H1) receptors were tested on three groups of guinea pig tracheal chains as follows; incubated trachea with: 1) indomethacin, 2) indomethacin, propranolol, and atropine and 3) indomethacin and propranolol. The EC50 (effective concentration of histamine causing 50% of maximum response) obtained in the presence of chlorpheniramine and all concentrations of the extract in all three groups were significantly greater than those of saline (p<0.05 to p<0.001) except low concentration of the extract in groups 1 and 3. The EC50 obtained in the presence of two higher concentrations of extract in group 2 were greater than group 1 and 3 (p<0.05 to p<0.001). Maximum response obtained in the presence of two higher concentrations of extract in group 2 were greater than those of group 1 and group 3 (p<0.001 for all cases). There were parallel right ward shift in concentration response curves obtained in the presence of only low and medium concentrations of the extract in group 2 compared to the those of saline. These results indicated an inhibitory effect of Crocus sativus at histamine H1 receptors.

Antiasthmatic effect of Nigella sativa in airways of asthmatic patients.

In the present study, the antiasthmatic (bronchodilatory) effect of the boiled extract of Nigella sativa in the airways of asthmatic patients was examined. The bronchodilatory effects of 50 and 100 mg/kg of boiled extract in comparison with 6 mg/kg theophylline were studied on 15 asthmatic patients. Pulmonary function tests (PFTs) including forced expiratory volume in one second (FEV(1)), peak expiratory flow (PEF), maximal mid expiratory flow (MMEF), maximal expiratory flow at 75, 50 and 25% of the FVC (MEF(75), MEF(50), and MEF(25,) respectively) and specific airway conductance (sGaw) were measured before administration and repeated , 30, 60, 90 120, 150, and 180 min after administration of the oral extract and theophylline. The results showed that the extract caused significant increases in all measured pulmonary function tests (PFTs), in most time intervals, (p<0.05 to p<0.001). However, the increase in FEV(1), MMEF and MEF(50) due to both doses of boiled extract and increase in MEF(75) and MEF(25) due to its lower doses were significantly lower than those of theophylline (p<0.05 to p<0.001). The onset of brochodilatory effect of extract was similar to that of theophylline beginning 30 min, and the effect of extract decline after 150 min following administration similar to the effect of theophylline. The effect of both doses of the extract was also significantly less than that of salbutamol at 30 minutes post administration (p<0.001 for all cases). The results of the present study showed that Nigella sativa has a relatively potent antiasthmatic effect on asthmatic airways. However, the effects of boiled extract of this plant on most measured PFTs was less than those of theophylline at concentrations used.

Stimulatory effect of Crocus sativus (saffron) on beta2-adrenoceptors of guinea pig tracheal chains.

To study the mechanism(s) of the relaxant effects of Crocus sativus (Iridaceae), the stimulatory effect of aqueous-ethanolic extracts of this plant and one of its constituent, safranal was examined on beta-adrenoceptors in tracheal chains of guinea pigs. The beta(2)-adrenergic stimulatory was tested by performing the cumulative concentration-response curves of isoprenaline-induced relaxation of pre-contracted isolated guinea pig tracheal chains. The studied solutions were included two concentrations of aqueous-ethanolic extract from Crocus sativus (0.1 and 0.2g%), safranal (1.25 and 2.5 microg), 10nM propranolol, and saline. The study was done in two different conditions including: non-incubated (group 1, n=9) and incubated tissues with 1 microM chlorpheniramine (group 2, n=6). The results showed clear leftward shifts in isoprenaline curves obtained in the presence of only higher concentration of the extract in group 1 and its both concentrations in group 2 compared with that of saline. The EC(50) (the effective concentration of isoprenaline, causing 50% of maximum response) obtained in the presence of both concentrations of the extract (0.17+/-0.06 and 0.12+/-0.02) and safranal (0.22+/-0.05 and 0.22+/-0.05) in group 1 and only in the presence of two concentrations of the extract (1.16+/-0.31 and 0.68+/-0.21) in group 2 was significantly lower compared to saline (1.00+/-0.22 and 4.06+/-1.04 for groups 1 and 2, respectively) (p<0.05-0.001). The maximum responses obtained in the presence of both concentrations of the extract and safranal in group 1 were significantly lower than that of saline (p<0.005 for all cases). All values (CR-1=(EC(50) obtained in the presence of active substances/EC(50), obtained in the presence of saline)-1) obtained in the presence of higher concentrations of extract in group 1, its both concentrations and higher concentration of safranal in group 2 were negative and there were significant differences in this value between propranolol and those obtained in the presence of extract and safranal (p<0.05 to p<0.001). The results indicated a relatively potent stimulatory effect of the extract from Crocus sativus on beta(2)-adrenoceptors which is partially due to its constituent, safranal. A possible inhibitory effect of the plant on histamine (H(1)) receptors was also suggested.

Effect of aqueous-ethanol extract from Crocus sativus (saffron) on guinea-pig isolated heart.

In this study, the effects of an aqueous-ethanol extract from Crocus sativus on heart rate and contractility were examined. Isolated guinea-pig hearts were perfused through the aorta in a Langendorff mode. Heart rate and contractility were determined in the presence of four concentrations of the extract (0.1, 0.5, 1.0 and 5.0 mg%) and diltiazem (0.1, 1, 10 and 100 microm) in perfused heart with: (1) ordinary Krebs solution (group 1, n = 9), (2) calcium-free Krebs solution (group 2, n = 7). In group 1, three higher concentrations of diltiazem (1, 10 and 100 microm), but only the highest (5.0 mg%) and two higher concentrations (1.0 and 5.0 mg%) of the extract caused significant reduction in heart rate and contractility, respectively (p < 0.05 to p < 0.001). In group 2, the highest (100 microm) and two higher concentrations (10 and 100 microm) of diltiazem (p < 0.05 to p < 0.01), but only the highest concentration of the extract showed significant reductions in the heart rate and contractility (p < 0.05 to p < 0.01). There were significant negative correlations between concentrations of the extract and diltiazem and their effects in both groups (p < 0.01 to p < 0.001). These results suggested a potent inhibitory effect of aqueous-ethanol extract from C. sativus on the calcium channel of guinea-pig heart.

The Effect of Exposure of Guinea Pig to Cigarette Smoke and their Sensitization in Tracheal Responsiveness to Histamine and Histamine Receptor (H(1)) Blockade by Chlorpheniramine.

Airway responsiveness to histamine and histamine H(1) receptor blockade by chlorpheniramine (CR-1) on guinea pig trachea were examined. Chronic obstructive pulmonary disease (COPD) and asthma were induced in guinea pigs by exposing them to cigarette smoke for 3 months and by sensitization with injection and inhalation of ovalbumin (OA). The responses of tracheal chains of COPD (n=8), COPD+asthma (n=6) and control animals (n=8) to histamine (EC(50) H) and (CR-1) were measured. The in vitro histamine responses of COPD and COPD+asthmatic guinea pigs in tracheal chains were significantly higher than those of control animals (p<0.001 and p<0.01, respectively). The CR-1 blockade was also significantly greater in trachea of COPD and COPD+asthma compared to that of controls (p<0.01 and p<0.05, respectively). There were significant correlations between EC(50) H and (CR-1) (r=-0.542, p<0.01). The hematocrit in COPD and COPD+asthma groups was also significantly higher than in controls (p<0.001 for both groups). The contractility of tracheal chains to histamine in COPD+asthma animals was significantly greater than those of control and COPD groups (p<0.05 for both cases). The differences in contractility between COPD and COPD+asthmatic groups, however, suggests different basic mechanisms for AHR in COPD and asthma.

Relaxant effect of Crocus sativus (saffron) on guinea-pig tracheal chains and its possible mechanisms.

As indicated in ancient Iranian medical books, Crocus sativus has therapeutic effects on respiratory diseases. The relaxant effect of this plant has been observed also on smooth muscles in previous studies. Therefore, in this study the relaxant effects of aqueous-ethanolic extracts of C. sativus and one of its main constituents, safranal, were examined on guinea-pig tracheal chains. The relaxant effects of four cumulative concentrations of aqueous-ethanolic extract (0.15, 0.3, 0.45, and 0.60 g %) and safranal (0.15, 0.30, 0.45, and 0.60 mL 0.2 mg mL(-1) solution) in comparison with saline, as negative control, and four cumulative concentrations of theophylline (0.15, 0.30, 0.45, and 0.60 mM), as positive control, were examined using guinea-pig precontracted tracheal chains. The tracheal chains had been precontracted by three different methods. Group 1 had been precontracted using 10 microM methacholine. The other two groups had been precontracted using 60 mM KCl at two different conditions: non-incubated tissues (group 2) and tissues incubated with 1 microM propranolol, 1 microM chlorpheniramine and 1 microM atropine (group 3) (for each group, n = 6). In group 1 all concentrations of theophylline, extract and safranal showed significant relaxant effects compared with saline (P < 0.05 to P < 0.001). In group 2 theophylline, extract and safranal showed concentration-dependent relaxant effects also compared with saline (P < 0.05 to P < 0.001 for different concentrations except two low concentrations of safranal). However, in group 3 the extracts of C. sativus showed a weak relaxant effect (P < 0.05 only for the highest concentration). The effects of the last concentration of safranal (0.60 mL 0.2 mg mL(-1) solution) in group 1, and all its concentrations in group 2 were significantly lower than those of theophylline (P < 0.05 to P < 0.001). In addition, the effects of safranal 0.45 and 0.60 mL 0.2 mg mL(-1) solution in groups 1 and 2 were significantly lower than that of C. sativus extract. There were significant correlations between the relaxant effects and concentrations for extract, safranal and theophylline in all experimental groups (P < 0.001 for all cases). These results showed a potent relaxant effect of C. sativus on tracheal chains of guinea-pigs that was comparable to or even higher than that of theophylline at the concentrations used. The results indicated that safranal was, at least in part, responsible for the relaxant effect of C. sativus.

Relaxant effects of Rosa damascena on guinea pig tracheal chains and its possible mechanism(s).

Several therapeutic effects including hypnotic, antispasmodic, treatment of abdominal and chest pain and strengthening the heart have been described for the flowers of Rosa damascena. Therefore in the present study, the relaxant effects of ethanolic extract and essential oils of Rosa damascena on tracheal chains of guinea pigs were examined. The relaxant effects of four cumulative concentrations of ethanolic extract (0.25, 0.5, 0.75, and 1.0g%) and essential oils (0.25, 0.5, 0.75, and 1.0vol.%) in comparison with saline as negative control and four cumulative concentrations of theophylline (0.25, 0.5, 0.75, and 1.0mM) were examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60mM KCl (group 1, n=5) and 10microM methacholine in two different conditions including: non-incubated tissues (group 2, n=8) and incubated tissues with 1microM propranolol and 1microM chlorpheniramine (group 3, n=5). In group 1 experiments two final concentrations of essential oil and theophylline and only final concentration of ethanolic extract showed relaxant effects compared to that of saline (p<0.01-0.001). In group 2 three higher concentrations of ethanolic extract and theophylline and all concentrations of essential oil showed concentration dependent relaxant effects compared to that of saline (p<0.05-0.001). In addition, the effect of 0.25 and 0.5g% of essential oils in group 2 was significantly higher than those of theophylline and ethanolic extract (p<0.01 for all cases). However, in group 3 experiments the extract and essential oil of Rosa damascena did not show any significant relaxant effect. There were significant correlations between the relaxant effects and concentrations for ethanolic extract and essential oil and theophylline in groups 1 and 2. These results showed a potent relaxant effect of Rosa damascena on tracheal chains of guinea pigs that was comparable to that of theophylline at concentrations used.

Relaxant effect of Thymus vulgaris on guinea-pig tracheal chains and its possible mechanism(s).

Thymus vulgaris for the treatment of respiratory diseases is indicated widely, and relaxant effects on smooth muscle have been shown previously. In the present study, the relaxant effects of macerated and aqueous extracts of Thymus vulgaris on tracheal chains of guinea-pigs were examined using cumulative concentrations of macerated and aqueous extracts in comparison with saline (as the negative control) and theophylline (as the positive control). The relaxant effects of four cumulative concentrations of macerated and aqueous extracts (0.25, 0.5, 0.75 and 1.0 g %) in comparison with saline (as the negative control) and four cumulative concentrations of theophylline (0.25, 0.5, 0.75 and 1.0 mm; as the positive control) were examined for their relaxant effects on precontracted tracheal chains of guinea-pig by 60 mm KCl and 10 microm methacholine in two different conditions: non-incubated tissues and incubated tissues with 1 microm propranolol and 1 microm chlorphenamine. There were significant correlations between the relaxant effects and the concentrations for both extracts and theophylline in all experimental groups (p < 0.01 to p < 0.001). These results demonstrated a potent relaxant effect of Thymus vulgaris on guinea-pig tracheal chains that was comparable to theophylline at the concentrations used.