RESUMO
Lung inflammation and alveolar enlargement are the major pathological conditions of chronic obstructive pulmonary disease (COPD) patients. Rice bran oil (RBO), a natural anti-inflammatory and antioxidative agent, has been used for therapeutic purposes in several inflammatory diseases. This study aimed to investigate the anti-inflammatory and antioxidative effect of RBO on a cigarette smoke extract (CSE)-induced emphysema model in mice. The results indicated that CSE significantly induced airspace enlargement in mouse lung. Increased inflammatory cells, macrophage, and TNF-alpha levels in bronchoalveolar lavage fluid (BALF) were noticed in CSE-treated mice. RBO (low and high dose)-supplemented mice showed decreased total BALF inflammatory cell, macrophage, and neutrophil numbers and TNF-alpha levels (p < 0.05). Additionally, the administration of RBO decreased the mean linear alveolar intercept (MLI) in the CSE-treated group. Additionally, RBO treatment significantly increased the total antioxidant capacity in both mouse BALF and serum. However, RBO did not have an effect on the malondialdehyde (MDA) level. These findings suggested that RBO treatment ameliorates lung inflammation in a CSE-induced emphysema mice model through anti-inflammatory and antioxidant pathways. Therefore, the supplementation of RBO could be a new potential therapeutic to relieve the severity of COPD.
Assuntos
Fumar Cigarros , Enfisema , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Camundongos , Animais , Antioxidantes/metabolismo , Pulmão/patologia , Óleo de Farelo de Arroz/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Fumar Cigarros/efeitos adversos , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Anti-Inflamatórios/uso terapêutico , Pneumonia/tratamento farmacológico , Líquido da Lavagem Broncoalveolar , Enfisema/induzido quimicamente , Enfisema/tratamento farmacológico , Produtos do TabacoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Oleo-gum resin of Commiphora wightii (Arnott) Bhandari of family Burseraceae, commonly known as 'guggul', is a well known Ayurvedic drug used traditionally to treat various disorders including respiratory ailments. However, role of C. wightii in chronic obstructive pulmonary disease (COPD) is not known. AIM: The present work was designed to investigate the protective potential of standardized C. wightii extract/and its fractions against elastase-induced COPD-linked lung inflammation and to identify key bioactive constituent(s). MATERIAL AND METHODS: C. wightii oleo-gum resin extract was prepared using Soxhlet extraction technique and the resultant extract was standardized on basis of guggulsterone content using HPLC. The extract was partitioned by different solvents in increasing order of polarity. Standardized extract/its partitioned fractions were orally administered to male BALB/c mice 1 h prior to intra-tracheal instillation of elastase (1U/mouse). Anti-inflammatory effect was evaluated by analyzing inflammatory cells and myeloperoxidase activity in lungs. The various fraction(s) were subjected to column chromatography to isolate bioactive compound. Isolated compound was identified using 1H and 13C-NMR and analyzed for assessment of several inflammatory mediators using techniques like ELISA, PCR, and gelatin zymography. RESULTS: C. wightii extract attenuated elastase-induced lung inflammation in dose-dependent manner and Ethyl acetate fraction (EAF) provided maximum protection. EAF was subjected to column chromatography followed by assessment of bioactivity of each sub-fraction, ultimately leading towards isolation of two compounds i.e. C1 and C2. C1 seems to be the key active principle of C. wightii, as it displayed significant anti-inflammatory activity against elastase induced lung inflammation while C2 largely remains ineffective. C1 was identified as mixture of E- and Z-guggulsterone (GS). Reduction in the elastase induced lung inflammation by GS was associated with downregulation of expression of several COPD linked pro-inflammatory factors such as IL-6/TNF-α/IL-1ß/KC/MIP-2/MCP-1/G-CSF as well as normalization of redox imbalance as indicated by levels of ROS/MDA/protein carbonyl/nitrite/GSH etc. Further, 21 days prolonged administration of GS (10 mg/kg b.wt; once daily) protected against elastase-induced emphysema by mitigating expression/activity of MMP-2/-9 and increasing TIMP-1 expression. CONCLUSION: Overall, guggulsterone seems to be the key bioactive constituent responsible for exerting beneficial effects of C. wightii against COPD.
Assuntos
Enfisema , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Masculino , Camundongos , Animais , Elastase Pancreática , Commiphora/química , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Enfisema Pulmonar/metabolismo , Enfisema/tratamento farmacológico , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/prevenção & controle , Anti-Inflamatórios/efeitos adversosRESUMO
BACKGROUND: Eucalyptol is a monoterpenoid oil present in many plants, principally the Eucalyptus species, and has been reported to have anti-inflammatory and antioxidative effects. HYPOTHESIS/PURPOSE: Since the potential effect of eucalyptol on mouse lung repair has not yet been studied, and considering that chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, the aim of this study was to investigate eucalyptol treatment in emphysematous mice. STUDY DESIGN: Male mice (C57BL/6) were divided into the following groups: control (sham-exposed), cigarette smoke (CS) (mice exposed to 12 cigarettes a day for 60 days), CSâ¯+â¯1â¯mg/ml (CS mice treated with 1â¯mg/ml eucalyptol for 60 days), and CSâ¯+â¯10â¯mg/ml (CS mice treated with 10â¯mg/ml eucalyptol for 60 days). Mice in the CS and control groups received vehicle for 60 days. Eucalyptol (or the vehicle) was administered via inhalation (15â¯min/daily). Mice were sacrificed 24â¯h after the completion of the 120-day experimental procedure. METHODS: Histology and additional lung morphometric analyses, including analysis of mean linear intercept (Lm) and volume density of alveolar septa (Vv[alveolar septa]) were performed. Biochemical analyses were also performed using colorimetric assays for myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) activity, in addition to using ELISA kits for the determination of inflammatory marker levels (tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1ß], interleukin 6 [IL-6], keratinocyte chemoattractant [KC], and tumor growth factor beta 1 [TGF-ß1]). Finally, we investigated protein levels by western blotting (nuclear factor (erythroid-derived 2)-like 2 [Nrf2], nuclear factor kappa B [NF-κB], matrix metalloproteinase 12 [MMP-12], tissue inhibitor of matrix metalloproteinase 1 [TIMP-1], neutrophil elastase [NE], and elastin). RESULTS: Eucalyptol promoted lung repair at the higher dose (10â¯mg/ml), with de novo formation of alveoli, when compared to the CS group. This result was confirmed with Lm and Vv[alveolar septa] morphometric analyses. Moreover, collagen deposit around the peribronchiolar area was reduced with eucalyptol treatment when compared to the CS group. Eucalyptol also reduced all inflammatory (MPO, TNF-α, IL-1ß, IL-6, KC, and TGF-ß1) and redox marker levels (MDA) when compared to the CS group (at least pâ¯<â¯0.05). In general, 10â¯mg/ml eucalyptol was more effective than 1â¯mg/ml and, at both doses, we observed an upregulation of SOD activity when compared to the CS group (pâ¯<â¯0.001). Eucalyptol upregulated elastin and TIMP-1 levels, and reduced neutrophil elastase (NE) levels, when compared to the CS group. CONCLUSION: In summary, eucalyptol promoted lung repair in emphysematous mice and represents a potential therapeutic phytomedicine in the treatment of COPD.
Assuntos
Enfisema/tratamento farmacológico , Eucaliptol/farmacologia , Fumar/efeitos adversos , Animais , Colágeno/metabolismo , Citocinas/metabolismo , Enfisema/induzido quimicamente , Enfisema/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Metaloproteinase 12 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Superóxido Dismutase/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
Diallyl disulfide (DADS) is the main organosulfur ingredient in garlic, with known antioxidant and anti-inflammatory activities. The aim of the present study was to investigate the effect of DADS on reducing the inflammation and redox imbalance in a rat emphysema model that was induced by intraperitoneal injection of cigarette smoke extract (CSE). Briefly, DADS exerted an anti-inflammation effect on emphysema rats through decreasing cell influx in the bronchoalveolar lavage fluid (BALF) and suppressing pro-inflammation cytokine production including tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) via inhibiting the NF-κB pathway. In addition, levels of oxidative stress markers including malondialdehyde (MDA) and myeloperoxidase (MPO) were reduced, while the activities of glutathione (GSH), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were markedly enhanced by DADS. Moreover, MMP-9 and TIMP-1 expression were down-regulated by DADS. Furthermore, the regulation effects of DADS on CD4⺠and CD8⺠T cells were observed. In conclusion, these encouraging findings suggest that DADS could be considered as a promising anti-inflammation and antioxidative agent for the treatment of emphysema.
Assuntos
Compostos Alílicos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Dissulfetos/farmacologia , Enfisema/tratamento farmacológico , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Regulação para Baixo , Enfisema/induzido quimicamente , Alho/química , Glutationa/sangue , Glutationa Peroxidase/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Malondialdeído/sangue , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/sangue , Ratos , Ratos Sprague-Dawley , Fumaça/efeitos adversos , Superóxido Dismutase/sangue , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Nicotiana/efeitos adversos , Fator de Necrose Tumoral alfa/sangueRESUMO
Exposure to ozone has led to airway inflammation and airway hyperresponsiveness, which potential mechanisms relate to ozone-induced oxidative stress. IL-17 is a growing target for autoimmune and inflammatory diseases. The aim of the study was to examine the inhibitory effects of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) on adverse effects of ozone which are noted above. After C57/BL6 mice were exposed to ozone (2.5ppm; 3h) for 12 times over 6 weeks, IL-17mAb, PBS was intraperitoneally injected into mice 1h after ozone or air exposure for 6 weeks and mice were studied 24h after final exposure, monitoring bronchial responsiveness, airway inflammatory cells, lung histology, levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage (BAL) fluid and serum, the expression of IL-17A mRNA and protein, glucocorticoid receptors (GR), and the phosphorylation of p38MAPK in lung tissues. The administration of IL-17mAb reduced the ozone-induced increases in total cells, especially neutrophils; decreased levels of cytokines, including IL-8 in BAL fluid, IL-8 and IL-17A in serum; mitigated the severity of airway hyperresponsiveness; attenuated lung inflammation scores and histologic analysis confirmed the suppression of lung inflammation, compared with the administration of a control PBS. Exposure to ozone results in increases in IL-17A production rate, mRNA and protein levels of IL-17A and the protein level of GR. These effects were halted and reversed by IL-17mAb treatment. Furthermore, IL-17mAb also reduced the phosphorylation of p38MAPK. Therefore, we conclude that IL-17mAb may be a useful therapy in ozone-related diseases, including COPD.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Interleucina-17/imunologia , Pneumonia/tratamento farmacológico , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/farmacologia , Brônquios/efeitos dos fármacos , Brônquios/patologia , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Doença Crônica , Citocinas/sangue , Enfisema/sangue , Enfisema/tratamento farmacológico , Enfisema/patologia , Enfisema/fisiopatologia , Interleucina-17/genética , Interleucina-17/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Ozônio , Pneumonia/sangue , Pneumonia/patologia , Pneumonia/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Potentially serious complications associated to emergency tracheotomy continue being a matter of concern. We review the pathogenesis of gas leakage in this setting and discuss about the possible mechanisms involved in its cause. We present two cases of pneumomediastinum, subcutaneous emphysema and pneumothorax in the context of emergency tracheotomy under spontaneous ventilation, finally resolved by chest drainage. The combination of overly negative pleural pressures due to extreme inspiratory efforts in the context of an almost completely obstructed airway together with over-pressurized alveoli because of gaseous entrapment secondary to serious expiratory obstruction appears to be the most plausible primary cause of air leaks in our patients. Understanding the underlying mechanisms evolved in its production will help clinicians to suspect and diagnose this phenomenon (AU)
Las complicaciones graves asociadas a la traqueotomía urgente continúan siendo un desafío clínico. En este trabajo revisamos y discutimos la fisiopatología de la fuga aérea en el contexto de la traqueotomía urgente. Presentamos dos casos de neumomediastino, enfisema subcutáneo y neumotórax en el curso de sendas traqueotomías urgentes realizadas sobre pacientes en ventilación espontánea que se resolvieron tras inserción de drenaje pleural. Nuestra conclusión es que la combinación de presiones pleurales inspiratorias muy negativas por el esfuerzo inspiratorio contra una vía aérea obstruida junto con la presencia de alveolos hiper-presurizados por el atrapamiento gaseoso espiratorio constituyen la base etiopatogénica del proceso. La comprensión de los mecanismos que subyacen en la generación del neumotórax y neumomediastino en este contexto facilitará que los clínicos sospechen y diagnostiquen el cuadro (AU)
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Traqueotomia/métodos , Diagnóstico de Pneumomediastino/métodos , Enfisema/complicações , Enfisema/tratamento farmacológico , Pneumotórax/tratamento farmacológico , Barotrauma/tratamento farmacológico , Barotrauma/terapia , Laringoscopia/tendências , Sucção/métodos , Anestesia Local/instrumentação , Anestesia Local/métodos , Anestesia Local , Radiografia TorácicaRESUMO
Aclidinium is a twice-daily long-acting muscarinic receptor antagonist (LAMA) with an interesting pharmacological profile. Recent evidence indicates that this LAMA, in addition to causing a significant improvement in lung function and other important supportive outcomes, such as health related quality of life, dyspnea and nighttime/early morning symptoms in patients suffering from COPD, is also able to significantly reduce the rate of exacerbations of any severity, is extremely effective in controlling the COPD symptoms, is able to reduce lung hyperinflation, and has an excellent cardiovascular safety profile. Consequently, aclidinium should be considered a first-line approach at least for the symptomatic treatment of COPD although there are still few head-to-head studies comparing this LAMA with other bronchodilators. In any case, aclidinium can be taken into account in the treatment of different COPD phenotypes (emphysema, chronic bronchitis, exacerbators and patients with overlap COPD asthma).
Assuntos
Espasmo Brônquico/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/administração & dosagem , Administração por Inalação , Espasmo Brônquico/etiologia , Bronquite Crônica/tratamento farmacológico , Bronquite Crônica/fisiopatologia , Enfisema/tratamento farmacológico , Enfisema/fisiopatologia , Humanos , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Tropanos/farmacologia , Tropanos/uso terapêuticoRESUMO
The development of emphysema in humans and mice exposed to cigarette smoke is promoted by activation of an adaptive immune response. Lung myeloid dendritic cells (mDCs) derived from cigarette smokers activate autoreactive Th1 and Th17 cells. mDC-dependent activation of T cell subsets requires expression of the SPP1 gene, which encodes osteopontin (OPN), a pleiotropic cytokine implicated in autoimmune responses. The upstream molecular events that promote SPP1 expression and activate mDCs in response to smoke remain unknown. Here, we show that peroxisome proliferator-activated receptor γ (PPARG/Pparg) expression was downregulated in mDCs of smokers with emphysema and mice exposed to chronic smoke. Conditional knockout of PPARγ in APCs using Cd11c-Cre Pparg(flox/flox) mice led to spontaneous lung inflammation and emphysema that resembled the phenotype of smoke-exposed mice. The inflammatory phenotype of Cd11c-Cre Pparg(flox/flox) mice required OPN, suggesting an antiinflammatory mechanism in which PPARγ negatively regulates Spp1 expression in the lung. A 2-month treatment with a PPARγ agonist reversed emphysema in WT mice despite continual smoke exposure. Furthermore, endogenous PPARγ agonists were reduced in the plasma of smokers with emphysema. These findings reveal a proinflammatory pathway, in which reduced PPARγ activity promotes emphysema, and suggest that targeting this pathway in smokers could prevent and reverse emphysema.
Assuntos
Enfisema/tratamento farmacológico , PPAR gama/metabolismo , Fumar/efeitos adversos , Tiazolidinedionas/farmacologia , Células Epiteliais Alveolares/metabolismo , Animais , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Células Dendríticas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Enfisema/etiologia , Enfisema/metabolismo , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Análise de Sequência com Séries de Oligonucleotídeos , Osteopontina/genética , Osteopontina/metabolismo , PPAR gama/agonistas , PPAR gama/genética , Tiazolidinedionas/uso terapêutico , TranscriptomaRESUMO
Chronic inhalation of cigarette smoke (CS) induces emphysema by the damage contributed by oxidative stress during inhalation of CS. Ingestion of açai fruits (Euterpe oleracea) in animals has both antioxidant and anti-inflammatory effects. This study compared lung damage in mice induced by chronic (60-day) inhalation of regular CS and smoke from cigarettes containing 100mg of hydroalcoholic extract of açai berry stone (CS + A). Sham smoke-exposed mice served as the control group. Mice were sacrificed on day 60, bronchoalveolar lavage was performed, and the lungs were removed for histological and biochemical analyses. Histopathological investigation showed enlargement of alveolar space in CS mice compared to CS + A and control mice. The increase in leukocytes in the CS group was higher than the increase observed in the CS + A group. Oxidative stress, as evaluated by antioxidant enzyme activities, mieloperoxidase, glutathione, and 4-hydroxynonenal, was reduced in mice exposed to CS+A versus CS. Macrophage and neutrophil elastase levels were reduced in mice exposed to CS + A versus CS. Thus, the presence of açai extract in cigarettes had a protective effect against emphysema in mice, probably by reducing oxidative and inflammatory reactions. These results raise the possibility that addition of açaí extract to normal cigarettes could reduce their harmful effects.
Assuntos
Arecaceae/química , Enfisema/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Líquido da Lavagem Broncoalveolar , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Cigarette smoke (CS) induces emphysema by tissue destruction through the production of oxidants and metalloproteinases [matrix metalloproteinases (MMPs)]. The possibility of lung repair after emphysema remains unclear. Our aim was to study the effects of vitamins C and E on mouse lung repair evaluated by catalase (CAT), superoxide dismutase (SOD) and MMP-9 activities; by the amount of tumor necrosis factor (TNF)-alpha in lung homogenates; by cell quantification in bronchoalveolar lavage (BAL) fluid; and by lung histology. Male C57BL/6 mice (n=25) were exposed to nine cigarettes per day, 7 days/week, for 60 days in a whole-body exposure chamber. The control group was sham smoked (n=10). After 60 days of CS exposure, a group of animals was sacrificed (n=5) and the others were divided into two groups: (a) CSv (n=10) supplemented with saline and olive oil (vehicles) for 60 days and (b) CSr (n=10) supplemented with vitamins C and E (50 mg/kg/day) for 60 days. These mice were then sacrificed; BAL was performed and the lungs were removed for biochemical and histological analysis. The results demonstrated that CAT activity was decreased in the CSv and CSr groups compared to the control group. SOD activity was higher in the CSv group than in the control and CSr groups. The CSv group showed a higher neutrophil count in BAL fluid, associated with more TNF-alpha in lung homogenates, than the control or CSr groups. Finally, emphysema in the CSv group was associated with fewer collagen and elastic fibers than in the control and CSr groups. These results indicate a possible role of vitamins C and E in lung repair after emphysema induced by long-term CS exposure in mice.
Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Enfisema/tratamento farmacológico , Vitaminas/uso terapêutico , Animais , Enfisema/induzido quimicamente , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fumar/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema. METHODS: One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema, defined by diffusing capacity of the lung for carbon monoxide (Dlco) [37.1 +/- 12.0% of predicted] and CT density mask (38.5 +/- 12.8% of voxels <- 910 Hounsfield units) [mean +/- SD] were enrolled into a randomized, double-blind, feasibility study at five university hospitals. Participants received all-trans retinoic acid (ATRA) at either a low dose (LD) [1 mg/kg/d] or high dose (HD) [2 mg/kg/d], 13-cis retinoic acid (13-cRA) [1 mg/kg/d], or placebo for 6 months followed by a 3-month crossover period. RESULTS: No treatment was associated with an overall improvement in pulmonary function, CT density mask score, or health-related quality of life (QOL) at the end of 6 months. However, time-dependent changes in Dlco (initial decrease with delayed recovery) and St. George Respiratory Questionnaire (delayed improvement) were observed in the HD-ATRA cohort and correlated with plasma drug levels. In addition, 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels. Retinoid-related side effects were common but generally mild. CONCLUSIONS: No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study. However, time- and dose-dependent changes in Dlco, CT density mask score, and health-related QOL were observed in subjects treated with ATRA, suggesting the possibility of exposure-related biological activity that warrants further investigation.
Assuntos
Enfisema/tratamento farmacológico , Isotretinoína/uso terapêutico , Ceratolíticos/uso terapêutico , Tretinoína/uso terapêutico , Idoso , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Enfisema/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Humanos , Isotretinoína/efeitos adversos , Isotretinoína/sangue , Ceratolíticos/efeitos adversos , Ceratolíticos/sangue , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Testes de Função Respiratória , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tretinoína/efeitos adversos , Tretinoína/sangueRESUMO
The effects of essential oil extracted from Nigella sativa (L.) seeds and its main components on human neutrophil elastase (HNE) activity were investigated. Essential oil was extracted from N. sativa (L.) seeds using hydrodistillation. The yield was equal to 0.4%. Inhibition of HNE activity by essential oil was found to be dose dependent. The highest inhibitory concentration (HIC) of essential oil which caused total inhibition of HNE activity was 5.8 mg/ml. Microassays carried out to evaluate the inhibitory effect of major components of essential oil on HNE activity revealed that carvacrol (5-isopropyl-2-methylphenol) showed marked HNE inhibitory activity with a very low IC(50) value (12 microM). Based on these results, the inhibitory effects of essential oil on HNE activity are due to the presence of bioactive molecules, mainly carvacrol this compound is an inhibitor of HNE and could be considered as a natural antielastase agent and possible candidate for phytotherapy in the treatment of injuries that appear in some pathologic cases such as chronic obstructive pulmonary disease and emphysema.
Assuntos
Elastase de Leucócito/antagonistas & inibidores , Monoterpenos/farmacologia , Nigella sativa/química , Óleos Voláteis/farmacologia , Cimenos , Relação Dose-Resposta a Droga , Enfisema/tratamento farmacológico , Humanos , Monoterpenos/isolamento & purificação , Monoterpenos/uso terapêutico , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/uso terapêutico , Fitoterapia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológicoAssuntos
Adjuvantes Imunológicos/uso terapêutico , Ácido Hialurônico/uso terapêutico , Lesão Pulmonar , Doenças Respiratórias/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/fisiologia , Animais , Arteriosclerose/tratamento farmacológico , Arteriosclerose/imunologia , Bronquite/tratamento farmacológico , Bronquite/imunologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Enfisema/tratamento farmacológico , Enfisema/imunologia , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Ácido Hialurônico/fisiologia , Pulmão/embriologia , Pulmão/imunologia , Peso Molecular , Faringite/tratamento farmacológico , Faringite/imunologia , Doenças Respiratórias/imunologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/imunologiaRESUMO
We investigated the effects of a novel oral neutrophil elastase inhibitor (ONO-6818) on acute lung injury and pulmonary emphysema induced by human neutrophil elastase (HNE). Young male Wistar rats were divided into four treatment groups: (1) control group (saline); (2) HNE group (HNE 200 U + 0.5% carboxymethyl-cellulose [solution for ONO-6818]); (3) low-dose ONO-6818 group (HNE 200 U + ONO-6818 10 mg/kg); and (4) high-dose ONO-6818 group (HNE 200 U + ONO-6818 100 mg/kg). Saline and HNE were applied via the trachea using a microsprayer. ONO-6818 was administered orally 1 hour before HNE application. Six hours after HNE application, neutrophil counts and hemoglobin concentration in bronchoalveolar lavage fluid and lung tissue myeloperoxidase activity were determined. Eight weeks after the application, FRC, TLC, lung compliance, and mean linear intercept were estimated. ONO-6818 attenuated dose-dependently HNE-induced increases in lung myeloperoxidase activity, hemoglobin, and neutrophil count in bronchoalveolar lavage fluid. Furthermore, it significantly attenuated HNE-induced increases in FRC, TLC, lung compliance, and mean linear intercept. ONO-6818 inhibited acute lung injury induced by HNE by minimizing lung hemorrhage and accumulation of neutrophils in the lung. ONO-6818 also inhibited the development of HNE-induced emphysematous changes including lung hyperinflation, degradation of elastic recoil, and airspace enlargement.
Assuntos
Modelos Animais de Doenças , Enfisema/tratamento farmacológico , Elastase de Leucócito/antagonistas & inibidores , Oxidiazóis/uso terapêutico , Pirimidinonas/uso terapêutico , Administração Oral , Animais , Líquido da Lavagem Broncoalveolar/citologia , Avaliação Pré-Clínica de Medicamentos , Enfisema/induzido quimicamente , Enfisema/patologia , Enfisema/fisiopatologia , Capacidade Residual Funcional/efeitos dos fármacos , Humanos , Contagem de Leucócitos , Elastase de Leucócito/efeitos adversos , Complacência Pulmonar/efeitos dos fármacos , Medidas de Volume Pulmonar , Masculino , Neutrófilos/efeitos dos fármacos , Oxidiazóis/farmacologia , Pirimidinonas/farmacologia , Ratos , Ratos Wistar , Mecânica Respiratória/efeitos dos fármacos , Escarro/enzimologiaRESUMO
Flavanol (-)epigallocatechin-3-gallate is shown to be a potent natural inhibitor of leukocyte elastase that may be used to reduce elastase-mediated progression to emphysema and tumor invasion. This phyto-factor, abundant in green tea, exerts a dose-dependent, noncompetitive inhibition of leukocyte elastase at a noncytotoxic concentration and is effective in neutrophil culture. This inhibition shows an IC(50) of 0.4 microM, 30 times higher than the alpha1-protease inhibitor but lower than other known natural and synthetic elastase inhibitors. The flavanol inhibits leukocyte elastase at concentrations of 50, 150, and 2500 times lower than that effective on gelatinases (MMP-2 and MMP-9), thrombin, and cathepsin G, respectively, and also blocks elastase-mediated activation of MMP-9.
Assuntos
Catequina/análogos & derivados , Catequina/farmacologia , Inibidores Enzimáticos/farmacologia , Elastase de Leucócito/antagonistas & inibidores , Neutrófilos/enzimologia , Catequina/uso terapêutico , Catepsina G , Catepsinas/antagonistas & inibidores , Células Cultivadas , Relação Dose-Resposta a Droga , Enfisema/tratamento farmacológico , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Gelatinases/antagonistas & inibidores , Humanos , Inflamação/tratamento farmacológico , Fitoterapia , Serina Endopeptidases , Trombina/antagonistas & inibidoresRESUMO
Bilateral emphysematous pyelonephritis is a rare condition, with only 14 cases reported in the English literature. It carries a bad prognosis, surgical management being the recommended mode of therapy. We report a case of bilateral emphysematous pyelonephritis in a 50-year-old diabetic lady which was successfully managed using antibiotics alone.