Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.312
Filtrar
1.
Life Sci ; 250: 117552, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32179074

RESUMO

AIMS: This study aimed to explore the possible mechanism of trauma-induced laryngotracheal stenosis and potential protective and therapeutic efficacy of quercetin on trauma-induced laryngotracheal stenosis. MAIN METHODS: The expression and activity of fibrotic factors [interleukin (IL)-6, IL-8, autophagy related 5 (ATG5), collagen (COL)-1, tumor growth factor (TGF)-ß COL-3, microtubule-associated proteins 1A/1B light chain 3A (LC3), and vascular endothelial growth factor (VEGF)] and fibrotic signaling mediators [mammalian target of rapamycin (mTOR) and phosphorylated AKT (pAKT)] were detected by real-time quantitative PCR (qRT-PCR), ELISA, Western blot, and immunohistochemical staining, respectively, in the lipopolysaccharide (LPS)-induced WI-38 (a human embryonic lung fibroblast cell line) cellular fibrotic model and a trauma-induced rabbit tracheal stenosis model, with and without quercetin treatment. KEY FINDINGS: Pre-treatment with quercetin significantly reversed the LPS-induced upregulation of pro-fibrotic factors (IL-6, IL-8, COL-1, COL-3, LC3) and fibrotic signaling mediators (mTOR and AKT), and it induced the downregulation of ATG5 in the WI-38 cells. Furthermore, the anti-fibrotic activity of quercetin was confirmed in the trauma-induced rabbit tracheal stenosis model. Thus, the nasogastric administration of quercetin attenuated the tracheal stenosis of the rabbit tracheal stenosis model, in addition to effectively reversing an increase in pro-fibrotic factors (VEGF, IL-6, TGF-ß, COL-1, and COL-3) and fibrotic signaling mediators (mTOR and AKT), as well as downregulating ATG5 of the rabbit tracheal stenosis model. SIGNIFICANCE: Quercetin exhibits anti-fibrotic activity by inhibiting pro-fibrotic factors and AKT/mTOR signaling pathway, in addition to activating autophagy activity. This study provided experimental evidence supporting the application of quercetin in tracheal stenosis, clinically.


Assuntos
Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Traqueia/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Autofagia , Linhagem Celular , Sobrevivência Celular , Constrição Patológica/tratamento farmacológico , Regulação para Baixo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Lipopolissacarídeos , Masculino , Coelhos , Transdução de Sinais , Traqueia/patologia
2.
Int J Vitam Nutr Res ; 90(1-2): 141-150, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30789805

RESUMO

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.


Assuntos
Curcuma , Pulmão/efeitos dos fármacos , Cloreto de Metacolina/farmacologia , Extratos Vegetais , Traqueia/efeitos dos fármacos , Animais , Pulmão/patologia , Cloreto de Metacolina/química , Ovalbumina , Extratos Vegetais/farmacologia , Ratos , Traqueia/patologia
3.
J Ethnopharmacol ; 246: 112162, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31419501

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia alnifolia Mart. & Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro" and "pedrécio", is used in folk medicine as antiseptic and to treat diseases that affect respiratory system, like bronchitis and asthma. AIM OF THE STUDY: The aim of this work was to investigate the spasmolytic activity and relaxant mechanism of the Lippia alnifolia essential oil (EOLA) on isolated guinea-pig trachea and to correlate with its use in folk medicine. MATERIALS AND METHODS: Leaves from L. alnifolia were collected in Pico das Almas, Chapada Diamantina, situated in the city of Rio de Contas, Bahia, Brazil. EOLA was extracted by hydrodistillation, analyzed by GC/FID and GC/MS and the volatile constituents were identified. Spasmolytic activity was assayed in isolated guinea-pig trachea pre-contracted with carbachol 1 µM or histamine 10 µM. Relaxant mechanism of EOLA was determined comparing concentration-response curves in the presence or absence of different blockers. RESULTS: Chemical analysis revealed the presence of carvone (60 ±â€¯0.8%) as major constituent. EOLA (1-243 µg/mL) relaxed isolated guinea-pig trachea pre-contracted with carbachol 1 µM [EC50 = 53.36 (44.75-63.51) µg/mL] or histamine 10 µM [EC50 = 5.42 (4.42-6.65) µg/mL]. The pre-incubation of 4-aminopyridine in histamine-induced contractions did not alter significantly the relaxant effect of EOLA. However, the presence of cesium chloride, glibenclamide, tetraethylammonium, propranolol, indomethacin, dexamethasone, hexamethonium, atropine, L-NAME, methylene blue or ODQ reduced EOLA relaxant effect. EOLA 18 µg/mL pre-incubation in calcium-free medium reduced histamine-evoked contractions, but did not alter histamine contractions in the presence of nifedipine. CONCLUSIONS: Lippia alnifolia essential oil has spasmolytic activity on isolated guinea-pig trachea and its mechanism of action possibly involves the activation of multiple signal transduction pathways, which culminate in potassium channels activation and cytosolic calcium reduction.


Assuntos
Lippia , Óleos Voláteis/farmacologia , Parassimpatolíticos/farmacologia , Traqueia/efeitos dos fármacos , Animais , Cálcio/metabolismo , Carbacol/farmacologia , Monoterpenos Cicloexânicos/farmacologia , Feminino , Cobaias , Técnicas In Vitro , Masculino , Óxido Nítrico/fisiologia , Folhas de Planta , Canais de Potássio/fisiologia , Receptores Adrenérgicos beta 2/fisiologia , Traqueia/fisiologia
4.
Medicine (Baltimore) ; 98(47): e17942, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764793

RESUMO

BACKGROUND: Anticholinergic administration prior to flexible bronchoscopy has been investigated, but studies have not yielded consistent results. METHODS: Patients were randomized 1:1 to receive nebulized 4 ml ipratropium bromide (1 mg, n = 125) or placebo (n = 125) for 15 minutes as premedication, 20 to 40 minutes before bronchoscopy. Airway secretions, bleeding, patient discomfort, procedure time, and procedure-related adverse events were compared between the groups. RESULTS: Nebulized ipratropium bromide prior to bronchoscopy could reduce airway secretions and patient discomfort (P = .02; P < .001, respectively), but not tracheobronchial bleeding or procedure time (P = .51, P = .36, respectively). Chest nodule or mass was the most common indication for performing bronchoscopy. The adverse events were higher in ipratropium bromide group, and hypertension was the most common complication. CONCLUSION: Nebulized ipratropium bromide prior to bronchoscopy is a more effective regimen that shows a practical benefit on the airway secretions and patient comfort, though these effects may not translate into any marked reduction in bleeding or of procedure time under general anesthesia. We suggest that routine nebulized ipratropium bromide premedication for bronchoscopy could be useful and beneficial. TRIAL REGISTRATION: chictr.org.cn: ChiCTR1800016881.


Assuntos
Secreções Corporais/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Broncodilatadores/administração & dosagem , Broncoscopia , Ipratrópio/administração & dosagem , Traqueia/efeitos dos fármacos , Administração por Inalação , Brônquios/fisiologia , Broncodilatadores/farmacologia , Método Duplo-Cego , Feminino , Humanos , Ipratrópio/farmacologia , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Pré-Medicação , Traqueia/fisiologia
5.
Toxicol Lett ; 316: 10-19, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31476341

RESUMO

Rapid risk assessment models for different types of cigarette smoke extract (CSE) exposure are critical to understanding the etiology of chronic obstructive pulmonary disease. The present study investigated inflammation of cultured tracheal tissues with CSE exposure. Rat trachea rings were isolated, cultured, then exposed to various concentrations of CSE from 3R4 F reference cigarettes for 4 h. Tissue/cellular morphology, ultrastructure, viability and damage, inflammatory cell infiltration, and inflammatory protein levels were measured and compared to untreated controls. Human bronchial epithelial cells (BEAS-2B) exposed to 0 or 300 µg/mL CSE were cocultured with macrophages to assess extent of mobilization and phagocytosis. Endotracheal epithelium cilia densities were significantly reduced with increasing CSE concentrations, while mucous membranes became increasingly disordered; both eventually disappeared. Macrophages became larger as the CSE concentration increased, with microvilli and extended pseudopodium covering their surface, and many primary and secondary lysosomes present in the cytoplasm. Inflammatory cell infiltration also increased with increasing CSE dose, as did intracellular adhesion molecule-1(ICAM-1), interleukin-6(IL-6). The method described here may be useful to qualitatively characterized the effects of the compound under study. Then, we use BEAS-2B cell line system to strength the observation made in the cultured tissues. Probably, an approach to integrate results from both experiments will facilitate its application. These results demonstrate that cultured rat tracheal rings have a whole-tissue structure that undergoes inflammatory processes similar to in vivo tissues upon CSE exposure.


Assuntos
Células Epiteliais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumaça/efeitos adversos , Fumar/efeitos adversos , Tabaco/efeitos adversos , Traqueia/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Humanos , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Macrófagos/ultraestrutura , Masculino , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Ratos Sprague-Dawley , Medição de Risco , Fatores de Tempo , Técnicas de Cultura de Tecidos , Traqueia/metabolismo , Traqueia/ultraestrutura
6.
Iran J Allergy Asthma Immunol ; 18(3): 320-331, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31522439

RESUMO

In this study we aimed to examine the relaxant effect of berberine, a compound extracted from a variety of herbs, on rat tracheal smooth muscle (TSM) and its possible mechanism(s). Cumulative concentrations of berberine (20, 65, 200 and 600 µg/mL) were added on pre-contracted TSM by methacholine or KCl in non-incubated or incubated tissues with atropine, chlorpheniramine, propranolol, diltiazem, glibenclamide, indomethacin, L-NG-nitro arginine methyl ester (L-NAME) and papaverine. The relaxant effects of theophylline (0.2, 0.4, 0.6 and 0.8 mM) as positive control and saline (1 mL) as negative control were also examined in non-incubated tissues. Berberine showed significant and concentration-dependent relaxant effects in non-incubated tissues contracted by KCl and methacholine (p<0.01 to p<0.001). There was no significant difference in the relaxant effects of berberine between non-incubated and incubated tissues with atropine, propranolol, diltiazem, glibenclamide, and papaverine. The relaxant effects of second concentrations of berberine in incubated tissues with L-NAME, its three lower concentration in incubated tissues with chlorpheniramine and its all concentrations in incubated tissues with indomethacin were significantly lower than non-incubated tissues (p<0.05 to p<0.001). The EC50 values of berberine in incubated tissues with chlorpheniramine was significantly higher than the non-incubated condition (p<0.05). Our findings reveal a relatively potent relaxant effect of berberine that is lower than the effect of theophylline. Proposed mechanisms for the relaxant effect of berberine are histamine (H1) receptor blockade, inhibition of cyclooxygenase pathways and/or nitric oxide formation.


Assuntos
Berberina/farmacologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Receptores Histamínicos H1/metabolismo , Transdução de Sinais , Animais , Berberina/química , Broncodilatadores/química , Broncodilatadores/farmacologia , Relação Dose-Resposta a Droga , Feminino , Masculino , Modelos Biológicos , Cloreto de Potássio/farmacologia , Ratos , Traqueia/efeitos dos fármacos , Traqueia/metabolismo
7.
J Med Food ; 22(9): 963-970, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31259654

RESUMO

Naringin and its aglycone, naringenin, occur naturally in our regular diet and traditional Chinese medicines. This study aimed to detect an effective therapeutic approach for cough variant asthma (CVA) through evaluating the relaxant effect of these two bioactive herbal monomers as antitussive and antiasthmatic on rat tracheal smooth muscle. The relaxant effect was determined by measuring muscular tension with a mechanical recording system in rat tracheal rings. Cytosolic Ca2+ concentration was measured using a confocal imaging system in primary cultured tracheal smooth muscle cells. In rat tracheal rings, addition of both naringin and naringenin could concentration dependently relax carbachol (CCh)-evoked tonic contraction. This epithelium-independent relaxation could be suppressed by BaCl2, tetraethylammonium, and iberiotoxin (IbTX), but not by glibenclamide. After stimulating primary cultured tracheal smooth muscle cells by CCh or high KCl, the intracellular Ca2+ increase could be inhibited by both naringin and naringenin, respectively. This reaction was also suppressed by IbTX. These results demonstrate that both naringin and naringenin can relax tracheal smooth muscle through opening big conductance Ca2+-activated K+ channel, which mediates plasma membrane hyperpolarization and reduces Ca2+ influx. Our data indicate a potentially effective therapeutic approach of naringin and naringenin for CVA.


Assuntos
Antiasmáticos/administração & dosagem , Antitussígenos/administração & dosagem , Asma/tratamento farmacológico , Flavanonas/administração & dosagem , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Extratos Vegetais/administração & dosagem , Traqueia/efeitos dos fármacos , Animais , Asma/genética , Asma/metabolismo , Asma/fisiopatologia , Cálcio/metabolismo , Citrus/química , Humanos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Masculino , Relaxamento Muscular/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traqueia/fisiopatologia
8.
Cancer Sci ; 110(8): 2485-2492, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31265162

RESUMO

Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 µg/mL MWCNT-7 or 0.250 µg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.


Assuntos
Neoplasias Pulmonares/induzido quimicamente , Pulmão/efeitos dos fármacos , Mesotelioma/induzido quimicamente , Nanotubos de Carbono/efeitos adversos , Neoplasias Pleurais/induzido quimicamente , Animais , Asbesto Crocidolita/efeitos adversos , Injeções Intraperitoneais/métodos , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Neoplasias Pleurais/patologia , Ratos , Ratos Endogâmicos F344 , Traqueia/efeitos dos fármacos , Traqueia/patologia
9.
Arch Pharm (Weinheim) ; 352(8): e1900002, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31353608

RESUMO

A series of 1,2,4-triazolo[1,5-a]pyrimidine derivatives was designed, synthesized, and screened for their phosphodiesterase (PDE 4B) inhibitory activity and bronchodilation ability. Compound 7e showed 41.80% PDE 4B inhibition at 10 µM. Eight compounds were screened for their bronchodilator activity, where compounds 7f and 7e elicited promising bronchodilator activity with EC50 values of 18.6 and 57.1 µM, respectively, compared to theophylline (EC50 = 425 µM). Molecular docking at the PDE 4B active site revealed a binding mode and docking scores comparable to those of a reference ligand, consistent with their PDE 4B inhibition activity.


Assuntos
Broncodilatadores/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Desenho de Fármacos , Músculo Liso/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/farmacologia , Pirimidinas/farmacologia , Traqueia/efeitos dos fármacos , Triazóis/farmacologia , Animais , Broncodilatadores/síntese química , Broncodilatadores/química , Relação Dose-Resposta a Droga , Humanos , Masculino , Simulação de Acoplamento Molecular , Estrutura Molecular , Contração Muscular/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/síntese química , Inibidores da Fosfodiesterase 4/química , Pirimidinas/síntese química , Pirimidinas/química , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
10.
BMC Complement Altern Med ; 19(1): 180, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331314

RESUMO

BACKGROUND: Fruit, bark and leaves of Zanthoxylum armatum DC are popular remedies for gastrointestinal, cardiovascular and respiratory disorders in the subcontinent traditional practices. The aim of the study was to individually probe the profile of methanol extracts from three different parts of Zanthoxylum armatum. METHODS: The ex-vivo muscle relaxant effects of extracts were assessed in the isolated intestine, trachea and thoracic aortic rings and were compared with the positive controls and CRC were constructed. The anti-diarrheal effect of extracts was evaluated in mice by inducing diarrhea with castor oil. The extracts were also studied for acute toxicity and butyrylcholine esterase inhibition. RESULTS: The extracts from fruit, bark and leaves of Z. armatum showed inhibitory effect against the butyrylcholine esterase enzyme with percent inhibition of 50.75 ± 1.23, 82.57 ± 1.33, and 37.52 ± 1.11respectively, compared to standard serine (IC50: 0.04 ± 0.001 µmol/L). The fruit and bark extracts provided 75, and 52% diarrheal protection, compared to verapamil (96%). In isolated rabbit jejunum strips, increasing addition of the extracts inhibited the spontaneous and high K+ precontractions with EC50 values of 0.71 and 3 mg/mL for fruit, EC50 values of 0.61 and 0.5 mg/mL for bark, EC50 0.81 and 3.1 mg/mL for leaves, like verapamil. The extracts induced a concentration-dependent relaxation of the carbachol (1 µM) and high K+ (80 mM) precontractions with EC50 values of 2.4 and 0.9 mg/mL for fruit, EC50 values of 1.2 and 3 for leaves. The bark extract was equipotent against both contractions with EC50 3.1 and 0.7 mg/mL, respectively. In the aortic rings, the fruit extract completely relaxed the phenylephrine (1 µM)-induced contractions with (EC50 value = 0.8 mg/ml) and a partial inhibition of high K+ induced contractions. The leaves extract completely relaxed the aortic contractions with (EC50 values = 1.0 and 8.5 mg/ml). The extracts caused no acute toxicity up to 3 g/kg dose. CONCLUSIONS: The experiments revealed that the extracts of aerial parts of Z. armatum have antidiarrheal properties in vivo and showed spasmolytic effect in intestinal and tracheal preparations with possible mechanism involving the blockage of Ca++ channels. These experiments provide enough justification for use of this plant in ethnomedicine in diarrhea, gut and bronchial spasms.


Assuntos
Inibidores Enzimáticos/farmacologia , Esterases/antagonistas & inibidores , Músculo Liso Vascular/efeitos dos fármacos , Parassimpatolíticos/química , Extratos Vegetais/farmacologia , Zanthoxylum/química , Animais , Antidiarreicos/química , Antidiarreicos/farmacologia , Aorta Torácica/efeitos dos fármacos , Inibidores Enzimáticos/química , Esterases/química , Frutas/química , Jejuno/efeitos dos fármacos , Masculino , Camundongos , Parassimpatolíticos/farmacologia , Casca de Planta/química , Extratos Vegetais/química , Folhas de Planta/química , Coelhos , Traqueia/efeitos dos fármacos
11.
J Physiol Pharmacol ; 70(1)2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31172971

RESUMO

Dexamethasone inhibits mucin secretion considering the primary option for treating acute asthma exacerbation. However, the mechanism underlying dexamethasone-induced decreased in mucosecretion is unclear. Recent studies have reported that dexamethasone exerts an inhibitory effect on mucosecretion in the lung by modulating the expression of calcium processing genes. However, the expression of the calcium processing genes in the trachea is not examined yet. Thus, the present study is the first to report the localization of calcium processing proteins such as transient receptor potential vanilloid-4 (Trpv4), transient receptor potential vanilloid-6 (Trpv6), calbindin-D9k (CaBP-9k) and plasma membrane Ca2+-ATPase 1 (Pmca1) in the mouse trachea and their glucocorticoid-induced response. In this study, mice were subcutaneously injected with dexamethasone for 5 days, and their tracheal samples were collected by dividing the trachea into the cervical, and thoracic sections based on its anatomical structure. The localization of TRPV4, TRPV6, CaBP-9k, and PMCA1 proteins was detected in the tracheal epithelium, submucosal glands, cartilages and muscles. Dexamethasone treatment downregulated the mRNA expression of the four calcium processing genes and mucin producing genes. The dexamethasone-induced decrease in the secretion of mucosubstances in the trachea was determined by performing Alcian blue-periodic acid-Schiff staining. Thus, the findings of the present study suggest that glucocorticoids simultaneously can regulate the expression of calcium processing genes and tracheal mucosecretion.


Assuntos
Dexametasona/farmacologia , Glucocorticoides/farmacologia , Mucosa Respiratória/efeitos dos fármacos , Animais , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Feminino , Masculino , Camundongos Endogâmicos C57BL , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/metabolismo , Mucosa Respiratória/metabolismo , Proteína G de Ligação ao Cálcio S100/genética , Proteína G de Ligação ao Cálcio S100/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Traqueia/efeitos dos fármacos , Traqueia/metabolismo
12.
J Ethnopharmacol ; 241: 112012, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31170518

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: There are report regarding therapeutic effects for Allium cepa L. (A. cepa) in Iranian traditional medicine and the plant has showed anti-inflammatory, anti-allergic, anti-hyperglycemic, antioxidant, anti-cancer, anti-hypertension, anti-hypercholesterolemia and anti-asthmatic activities in previous studies. AIM OF THE STUDY: In this study, the contribution of ß2 adrenergic, muscarinic and histamine (H1) receptors, calcium and potassium channels, and cyclooxygenase pathway in the relaxant effect of A. cepa extract on tracheal smooth muscle (TSM) was assessed. MATERIALS AND METHODS: TSM was contracted by KCl (60 mM) or methacholine (10 µM) for 5 min and cumulative concentrations of A. cepa extract (2, 4, 8, 16, 32 and 64 mg/ml) were added to organ bath every 5 min. Theophylline (0.2, 0.4, 0.6 and 0.8 mM) as positive control, and saline (1 ml) as negative control were also examined in non-incubated tissues. The relaxant effect of A. cepa extract was examined on non-incubated and incubated TSM with propranolol, chlorpheniramine, diltiazem, atropine, glibenclamide and indomethacin. RESULTS: A. cepa showed concentration-dependent relaxant effects on non-incubated TSM contracted by KCl (60 mM) or methacholine (10 µM), (P < 0.01 to p < 0.001). There was no significant difference in the relaxant effects of A. cepa between non-incubated and incubated tissues with glibenclamide, atropine, chlorpheniramine and indomethacin. The plant extract showed significant lower relaxant effects in incubated TSM with propranolol and diltiazem compared to non-incubated tissues. EC50 values of A. cepa extract in incubated TSM with propranolol and diltiazem were significantly lower than non-incubated tissues (p < 0.001 and p < 0.05, respectively). The relaxant effects of different concentrations of the extract of A. cepa were not significantly different with those of theophylline. The concentrations of A. cepa extract and theophylline were significant correlated with their relaxant effects (p < 0.05 to p < 0.001). In incubated TSM with propranolol and diltiazem, concentration ratio minus one (CR-1) values was positive (2.65 ±â€¯0.63 and 1.28 ±â€¯0.43 respectively). CONCLUSION: The A. cepa extract showed relatively potent relaxant effect on TSM which was comparable to the effect of theophylline. The results showed that ß2-adrenergic stimulatory and/or calcium channel blockade are the possible mechanisms for the relaxant effects of the plant.


Assuntos
Proteínas de Membrana/fisiologia , Músculo Liso/efeitos dos fármacos , Cebolas , Parassimpatolíticos/farmacologia , Extratos Vegetais/farmacologia , Prostaglandina-Endoperóxido Sintases/fisiologia , Traqueia/efeitos dos fármacos , Animais , Masculino , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Traqueia/fisiologia
13.
J Pharmacol Exp Ther ; 370(1): 127-136, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31085697

RESUMO

AZD8871 is a novel muscarinic antagonist and ß 2-adrenoceptor agonist in development for chronic obstructive pulmonary disease. This study describes the pharmacological profile of AZD8871 in in vitro and in vivo assays. AZD8871 is potent at the human M3 receptor (pIC50 in binding assays: 9.5) and shows kinetic selectivity for the M3 (half-life: 4.97 hours) over the M2 receptor (half-life: 0.46 hour). It is selective for the ß 2-adrenoceptor over the ß 1 and ß 3 subtypes (3- and 6-fold, respectively) and shows dual antimuscarinic and ß 2-adrenoceptor functional activity in isolated guinea pig tissue (pIC50 in electrically stimulated trachea: 8.6; pEC50 in spontaneous tone isolated trachea: 8.8, respectively), which are sustained over time. AZD8871 exhibits a higher muscarinic component than batefenterol in human bronchi, with a shift in potency under propranolol blockade of 2- and 6-fold, respectively, together with a persisting relaxation (5.3% recovery at 8 hours). Nebulized AZD8871 prevents acetylcholine-induced bronchoconstriction in both guinea pig and dog with minimal effects on salivation and heart rate at doses with bronchoprotective activity. Moreover, AZD8871 shows long-lasting effects in dog, with a bronchoprotective half-life longer than 24 hours. In conclusion, these studies demonstrate that AZD8871 is a dual-acting molecule with a high muscarinic component and a long residence time at the M3 receptor; moreover, its preclinical profile in animal models suggests a once-daily dosing in humans and a favorable safety profile. Thus, AZD8871 has the potential to be a next generation of inhaled bronchodilators in respiratory diseases.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/farmacologia , Quinolinas/efeitos adversos , Quinolinas/farmacologia , Receptor Muscarínico M3/antagonistas & inibidores , Receptores Adrenérgicos beta 2/metabolismo , Segurança , Triazóis/efeitos adversos , Triazóis/farmacologia , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/farmacocinética , Animais , Brônquios/efeitos dos fármacos , Brônquios/fisiologia , Sistema Cardiovascular/efeitos dos fármacos , Cães , Cobaias , Humanos , Masculino , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/farmacocinética , Quinolinas/administração & dosagem , Quinolinas/farmacocinética , Receptor Muscarínico M2/metabolismo , Distribuição Tecidual , Traqueia/efeitos dos fármacos , Traqueia/fisiologia , Triazóis/administração & dosagem , Triazóis/farmacocinética
14.
Biol Pharm Bull ; 42(5): 703-711, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061312

RESUMO

Cigarette smoke is a well-known strong risk factor for inducing airway hyperreactivity (AHR), but the underlying molecular mechanisms are not fully understood. In the present study, mouse in-vivo and in-vitro models were used to study effects of dimethyl sulfoxide (DMSO)-extracted cigarette smoke particles (DSP) on the airway, and to explore the underlying molecular mechanisms that are involved in DSP-induced AHR. In mouse in-vivo model, DSP (0.75, 1.5 or 3 µL/mL) was administered intranasally daily for 7 d. At the end of this period, lung functions were measured with flexiVent™. The results showed that the mice exhibited AHR in a dose-dependent manner following methacholine inhalation in vivo. In mouse in-vitro organ culture model, exposure of mouse tracheal segments to DSP (0.1 µL/mL) with or without the following pharmacological inhibitors: specific c-Jun-N-terminal kinase (JNK) inhibitor SP600125 (10 µM) or the anti-inflammatory drug dexamethasone (1 µM). DSP-induced bradykinin receptor-mediated airway contraction with increased mRNA and protein expressions for bradykinin B1 and B2 receptors could be significantly reduced by SP600125 or dexamethasone. In conclusion, the present study demonstrates that DSP could induce AHR in vivo and in vitro. In addition to this, the upregulation of bradykinin receptors in airway is most likely one of the underlying molecular mechanisms involved.


Assuntos
Hiper-Reatividade Brônquica/induzido quimicamente , Fumaça/efeitos adversos , Tabaco/efeitos adversos , Animais , Antracenos/farmacologia , Anti-Inflamatórios/farmacologia , Dexametasona/farmacologia , Dimetil Sulfóxido/química , Proteínas Quinases JNK Ativadas por Mitógeno/fisiologia , Masculino , Camundongos Endogâmicos BALB C , Receptor B1 da Bradicinina/fisiologia , Receptor B2 da Bradicinina/fisiologia , Solventes/química , Traqueia/efeitos dos fármacos , Traqueia/fisiologia
15.
J Ethnopharmacol ; 239: 111915, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31039428

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Adenophora triphylla var. japonica is frequently used as an oriental medicinal plant in Korea, China, and Japan for its anti-inflammatory, antitussive, and hepatoprotective effects. AIM OF THE STUDY: In the present study, the antitussive, expectorant, and anti-inflammatory effects of AR powder were investigated using animal models to evaluate their potential to treat respiratory disorders. MATERIALS AND METHODS: AR powder was administered orally to mice once daily for 11 days, at dose levels of 400, 200, and 100 mg/kg. Theobromine (TB), ambroxol (AM) and dexamethasone (DEXA) were used as standard drugs for antitussive effects, expectorant effects and anti-inflammatory effects, respectively. Evaluations of antitussive effects were based on changes in body weight, the number of cough responses and the histopathology of the lung and trachea. Expectorant effects were based on changes in the body weight, macroscopic observations of body surface redness, the mucous secretion of the trachea and histopathology of lung (secondary bronchus). Anti-inflammatory effects were based on changes in the body weight, macroscopic observations involving redness and edema of the treated ear, absolute and relative ear weights and histopathology of the treated ears. RESULTS: Allergic acute inflammation and coughing induced by exposure to NH4OH and symptoms of xylene-induced contact dermatitis were significantly inhibited by treatment with AR powder in a dose-dependent manner. Histological analyses revealed that AR powder decreased the OD values in trachea lavage fluid, reduced body surface redness, thicknesses of intrapulmonary secondary bronchus mucosa, and the number of PAS-positive mucous producing cells. Overall, AR powder administered at 200 mg/kg displayed superior antitussive and expectorant effects as compared to TB (50 mg/kg), and AM (250 mg/kg). At the highest concentration (400 mg/kg) AR powder displayed only moderately improved anti-inflammatory activities as compared to DEXA (1 mg/kg). CONCLUSION: The results obtained in this study suggest that AR powder exerts dose-dependent, favorable antitussive, expectorant, and anti-inflammatory activities achieved through modulation of the activity of mast cells and respiratory mucous production. Therefore, AR powder may serve as a therapeutic agent in various respiratory disorders, especially those that occur as a result of environmental toxicants.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antitussígenos/uso terapêutico , Campanulaceae , Tosse/tratamento farmacológico , Dermatite de Contato/tratamento farmacológico , Expectorantes/uso terapêutico , Hidróxido de Amônia , Animais , Tosse/induzido quimicamente , Tosse/metabolismo , Tosse/patologia , Dermatite de Contato/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos Endogâmicos ICR , Muco/efeitos dos fármacos , Muco/metabolismo , Raízes de Plantas , Pós , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Traqueia/efeitos dos fármacos , Traqueia/patologia , Xilenos
16.
Eur J Pharmacol ; 853: 229-235, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30935895

RESUMO

Our previous study found that the anthelmintic drug niclosamide relaxed the constricted arteries and inhibited proliferation and migration of vascular smooth muscle cells. Here, we investigated the effect of niclosamide ethanolamine (NEN) on trachea function and the proliferation and migration of trachea smooth muscle cells. Isometric tension of trachea was recorded by multi-channel myograph system. The cell proliferation was detected by using BrdU cell proliferation assay. The cell migration ability was evaluated by using scratch assay. The protein level was measured by using western blot technique. Acute treatment with NEN dose-dependently relaxed acetylcholine chloride (Ach)- and High K+ physiological salt solution (KPSS)-induced constriction of mice trachea. Pre-treatment with NEN inhibited Ach- and KPSS-induced constriction of mice trachea. NEN treatment inhibited proliferation of human bronchial smooth muscle cells (HBSMCs), inhibited migration of HBSMCs and rat primary trachea smooth muscle cells. NEN treatment activated adenosine monophosphate activated protein kinase (AMPK) activity and inhibited signal transducer and activator of transcription 3 (STAT3) activity in HBSMCs. In conclusion, niclosamide ethanolamine induces trachea relaxation and inhibits proliferation and migration of trachea smooth muscle cells, indicating that niclosamide might be a potential drug for chronic asthma treatment.


Assuntos
Movimento Celular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Niclosamida/farmacologia , Traqueia/efeitos dos fármacos , Traqueia/fisiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Acetilcolina/farmacologia , Animais , Brônquios/citologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Potássio/farmacologia , Ratos , Traqueia/citologia , Vasoconstrição/efeitos dos fármacos
17.
Environ Toxicol Pharmacol ; 68: 155-163, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30986632

RESUMO

OBJECTIVE: To observe the effects of prolonged exposure to high concentrations of PM2.5 on the trachea and lungs of mice and to determine whether the damages to the trachea and lung are induced by necroptosis. METHODS: Six- to eight-week-old female Balb/C mice of PM group were restrained in an animal restraining device using a nose-only "PM2.5 online enrichment system" for 8 weeks, in Shijiazhuang, Hebei, China. Anti -Fas group was exposed to PM2.5 inhalation and anti-Fas treatment via intranasal instillation. The mice in the control group inhaled filtered clean air. PM2.5 sample was collected and analyzed. Airway Hyperresponsiveness (AHR) was tested. Lung tissue and bronchoalveolar lavage fluid (BALF) were analyzed for Hematoxylin and eosin (HE) staining, electron microscopy, cellular inflammation, cytokines, Tunel, Fas, RIPK3 and MLKL expression. RESULTS: Compared to the other two groups, PM group displayed significantly increased AHR, neutrophils in BALF, significant bronchitis and alveolar epithelial hyperplasia and inflammation and necroptosis which were indicated by increased TUNEL, Fas, RIPK3 and MLKL measure. CONCLUSION: Our findings suggest that PM2.5 can enhance AHR and these changes are induced by necroptosis-related inflammation.


Assuntos
Poluentes Atmosféricos/toxicidade , Material Particulado/toxicidade , Hipersensibilidade Respiratória/induzido quimicamente , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/metabolismo , Feminino , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiologia , Pulmão/ultraestrutura , Camundongos Endogâmicos BALB C , Necrose/induzido quimicamente , Necrose/metabolismo , Necrose/patologia , Necrose/fisiopatologia , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Hipersensibilidade Respiratória/fisiopatologia , Traqueia/efeitos dos fármacos , Traqueia/patologia , Traqueia/fisiologia , Traqueia/ultraestrutura
18.
Mater Sci Eng C Mater Biol Appl ; 101: 1-14, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029302

RESUMO

Tracheal reconstruction remains a major surgical challenge, mainly owing to the scarce of resilient hollow grafts with identifiable vascular pedicle in humans. In this study, we developed a three-layer, elastomeric, trachea-like composite made of poly glycerol sebacate (PGS) and polycaprolactone (PCL), which presented appropriate resilient property, timely degradation and interconnected pores. C shape PCL rings fabricated with selective laser sintering (SLS) techniques are regularly positioned around porous PGS tubes and fixed by PCL electrospinning sheath. Such an elastomeric composite underwent host remodeling including rapid vascularization and tissue infiltration after fascia wrapping. With degrading of PGS, C rings well incorporated into growing fascia and lead to the formation of pedicled tracheal grafts, which attributes to the strong and resilient properties of generated hollow grafts thus enabled orthotopic transplantation in segmental tracheal defect. Progressive remodeling on such vascularized and mechanically stable grafts resulted in epithelium regeneration on luminal side as well as production of adequate amount of collagen and elastin, which warrantees the air passage during breathing. Future study employing large animal models more representative of human tracheal regeneration is warranted before clinical translation. Using fast degrading PGS combined with PCL rings represents a philosophical shift from the prevailing focus on tough grafts in airway reconstruction and may impact regenerative medicine in general.


Assuntos
Prótese Vascular , Elastômeros/farmacologia , Fáscia/irrigação sanguínea , Regeneração/efeitos dos fármacos , Stents , Tecidos Suporte/química , Traqueia/fisiologia , Animais , Implante de Prótese Vascular , Decanoatos/farmacologia , Epitélio/efeitos dos fármacos , Fáscia/efeitos dos fármacos , Glicerol/análogos & derivados , Glicerol/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Poliésteres/farmacologia , Polímeros/farmacologia , Porosidade , Coelhos , Traqueia/efeitos dos fármacos , Traqueia/ultraestrutura
19.
Iran J Allergy Asthma Immunol ; 18(1): 12-26, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30848570

RESUMO

Medicinal plants have been identified and used as primary sources in prevention and treatment of pulmonary diseases (mainly obstructive pulmonary diseases) from ancient times due to various pharmacological activities. In this review, the stimulatory effects of extracts, some fractions and constituents of medicinal plants on ß2-adrenoceptors which could be used as possible therapeutic agents in the future were reviewed. Various databases including; Medline, PubMed, ScienceDirect, Scopus, and Google Scholar were searched using stimulatory effect, ß2-adrenoceptors, possible mechanism, tracheal smooth muscle (TSM), medicinal plants and their constituents as keywords from 1985 to 2017. All studied plants including; Nigella sativa, Rosa damascena, Thymus vulgaris, Carum copticom, Carum carvi, Zataria multiflora, Crocus sativus, Cuminum cyminum, Liomnia acidissima, Portulaca oleraceae, Satureja hortensis, Ephedra sinica and Achillea millefolium showed relaxant effect on tracheal smooth muscle with a stimulatory effect on ß2-adrenoceptors mechanism. The studied plants and their constituents could be of therapeutic value in clinical practice as a bronchodilatory drug by ß2-adrenoceptors stimulatory mechanism for treatment of obstructive pulmonary diseases.


Assuntos
Músculo Liso/efeitos dos fármacos , Extratos Vegetais/farmacologia , Receptores Adrenérgicos beta 2/fisiologia , Traqueia/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Antagonistas de Receptores Adrenérgicos beta 2/farmacologia , Animais , Humanos , Músculo Liso/fisiologia , Plantas Medicinais , Traqueia/fisiologia
20.
Iran J Allergy Asthma Immunol ; 18(1): 48-61, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30848573

RESUMO

Epidemiological and clinical studies have demonstrated a close association between obesity and asthma. The current study investigated the effect of high-fat diet on tracheal responsiveness to methacholine and insulin resistance in ovalbumin (OVA) sensitized male and female rats. The rats were divided into eight groups (n=6 per group): female with the normal diet (F+ND), male with the normal diet (M+ND), female OVA-sensitized with the normal diet (F+SND), male OVA-sensitized with the normal diet (M+SND), female with high-fat diet (F+HFD), male with high-fat diet (M+HFD), female OVA-sensitized with high-fat diet (F+SHFD), and male OVA-sensitized with high-fat diet (M+SHFD). All rats were fed for 8 weeks with high-fat diet or standard pelts, and for another 4 weeks, they were sensitized with OVA or saline. At the end of the study, the tracheal responsiveness to methacholine, serum insulin, and blood glucose levels was measured. Also, insulin resistance indexes were determined. OVA-sensitization and diet-induced obesity caused the curve of methacholine concentration response to shifting to the left. In addition, results indicated that the EC50 (the effective concentration of methacholine generating 50% of peak response) in F+SHFD rats was statistically lower than M+SHFD group (p<0.05). Moreover, insulin resistance was higher in the F+SHFD than the M+SHFD group (p<0.001). These results suggest that insulin resistance and metabolic syndrome may be involved in the pathogenesis of obesity associated with OVA-sensitized rats condition, especially in female animals.


Assuntos
Asma/fisiopatologia , Broncoconstritores/farmacologia , Dieta Hiperlipídica , Resistência à Insulina , Cloreto de Metacolina/farmacologia , Obesidade/fisiopatologia , Traqueia/efeitos dos fármacos , Alérgenos , Animais , Glicemia/análise , Modelos Animais de Doenças , Feminino , Insulina/sangue , Masculino , Ovalbumina , Ratos Wistar , Traqueia/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA