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- ItemSomente MetadadadosAvaliação dos efeitos dos componentes dos óleos essenciais (timol, carvacrol e p-cimeno) no enfisema pulmonar induzido por instilação de elastase em camundongos(Universidade Federal de São Paulo, 2016-03-23) Pereira, Ellen Games Jacob [UNIFESP]; Prado, Carla Maximo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Pulmonary emphysema is the most important component of Chronic Obstructive Pulmonary Disease (COPD) and is characterized by destruction of alveolar walls resulting in an enlargement and progressively airflow limitation. Although COPD represents the fourth leading cause of mortality in the world there is still no specific therapeutic measures for the treatment, which is still symptomatic. Phytotherapy, including essential oils, is widely used to treat various diseases, however, in most cases, there is not enough scientific evidence. Objective: To evaluate the effects of treatment with thymol, carvacrol and p-cymene, monoterpenes derived from essential oils of Brazilian plant species, the changes in respiratory mechanics and pulmonary histopathology induced by instillation of elastase. Methodology: Male C57BL6 mice were used, which were given saline or elastase. 30 minutes after instillation of elastase animals were treated with thymol, carvacrol, p-cymene or vehicle. These treatments were repeated on days 7, 14, 21 and 28. Animals that received saline were treated with vehicle only. On the 28th, after 30 minutes of treatment they were evaluated: mechanics of the respiratory system; exhaled nitric oxide (NoEx), pulmonary inflammation and cytokines in the bronchoalveolar lavage (BAL), evaluation of the content of collagen fibers and alveolar diameter and expression of MMP-9, TIMP-1, NF-kB and 8-iso-PGF- 2? by immunohistochemistry. Statistical analysis was performed using the SigmaStat using analysis of variance One way ANOVA. Results: The elastase group had pulmonary emphysema (increase of Lm), an increase of macrophages and IL-6, IL-8, IL-1? and IL-17 levels in BAL, in addition to increased deposition of fibers collagen and expression of MMP-9, TIMP-1, isoprostane and NF-kB in the lung parenchyma. Still, there was an increase of NoEx these animals. The treatments with thymol, carvacrol and p-cymene reduced pulmonary inflammation, the cytokines IL-6, IL-8, IL-17 and IL-1? the values Lm and collagen deposition in the lung parenchyma, as well as MMP-9 expression, NF-KB and isoprostane in lung tissue. TIMP 1 levels in the treated groups were higher than the control group but similar to animals receiving no treatment elastase. Treatment with thymol still reduced exhaled NO. Conclusion: These compounds reduced the inflammation and tissue destruction attenuated and reduced collagen deposition associated with MMP-9 reduced. These effects can be attributed to reduced NF-kB expression of pro-inflammatory cytokines (IL-17, IL-1?) and also reduce oxidative stress. Apparently, the position or the hydroxyl radical presence does not interfere with the biological effects of these compounds in the emphysema model. Other mechanisms of action have yet to be evaluated.
- ItemAcesso aberto (Open Access)Avaliação dos efeitos dos constituintes de óleos essenciais (timol, carvacrol e p-cimeno) na inflamação pulmonar aguda induzida por instilação de LPS em camundongos(Universidade Federal de São Paulo, 2015-05-05) Guerreiro, Marina Pinheiro [UNIFESP]; Prado, Carla Maximo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The acute respiratory distress syndrome (ARDS) is characterized by a diffuse inflammatory response, due to activation of pro-inflammatory agents and oxidants. Despite the high mortality, which affects 40% of patients, there are no specific therapeutic tool for the treatment, which is still based in protective ventilation and in the treatment of the underlying disease and the use of corticosteroids. Extensive research and the elucidation of the mechanisms involved in compounds extracted from plants have been great scientific interest, since many biological effects are shown related to the treatment with medicinal pants. Aim: 1. To evaluate the effects of treatment with thymol, carvacrol and p-cymene, monoterpenes, derived from essential oils of Lippia gracillis e L. sidoides plants, in respiratory mechanics and pulmonary histopathology in an experimental model of acute lung injury (ALI); 2. To evaluate if the presence and/or the position of hydroxyl radical in the chemical structure interferes in the bioactivity of these compounds in the model studied. Methods: Male Balb/c mice received LPS or saline intratracheally. After 6 hours of instillation, animals were treated with thymol, carvacrol, p-cymene (doses of 10, 15 and 20 mg / kg intranasal), dexamethasone (5 mg / kg intraperitoneally) or vehicle. After 24 hours from the time of LPS instillation we evaluated: the respiratory mechanics; inflammatory cells in the bronchoalveolar lavage (Bhavnani and Ballow) and peripheral blood, and total protein levels and proinflammatory cytokines in BALF, isoprostane, NF-?B, and the amount of collagen fibers in the lung tissue. Results: We show first that 6 hours after instillation of LPS, the animals had increased pulmonary inflammation compared to the control, and that this response increased in 24 hours, however changes in lung mechanics occurred only in 24 hours. Then we determined by means of a dose response curve, that 20mg/Kg was the most effective dose for the reduction of neutrophils for the three compounds evaluated. We observed that treatment with the three components of essential oils improved the respiratory function, reduced the amount of inflammatory cells in peripheral blood and BALF. Moreover, these treatments reduced the total protein content, IL-8 and IL-6 in BALF, the amount of collagen fibers and in the positive area of isoprostane in lung tissue. The cytokine IL-1? was not reduced by p-cymene compound and none of the compounds altered the levels of TNF-?. Moreover, thymol and carvacrol significantly reduced expression of P-65-NF-?B in the lung. These results were similar to those obtained with treatment with dexamethasone. Conclusion: Thymol and Carvacrol showed anti-inflammatory effect in a model of ALI, reducing pro-inflammatory cytokines, oxidative stress and inhibiting the activation of p-65-NF-?B, suggesting that the position of the hydroxyl group in the chemical structure does not interfere with the biological effect in this experimental model. Although the p-cymene compound, which has no hydroxyl group in its chemical structure, has reduced lung inflammation and oxidative stress, the mechanisms involved were different from those observed in thymol and carvacrol, since it had no effect on the expression of NF -?B and levels of IL-1? in lung. Together our results suggest that these compounds have significant therapeutic interest to treat inflammatory lung diseases, particularly ARDS and further studies are needed to clarify the exactly mechanisms of action and the importance of the hydroxyl in its structure.
- ItemAcesso aberto (Open Access)Estudo da interação do gama-terpineol em filmes de Langmuir como modelos de membrana(Universidade Federal de São Paulo, 2021-01-29) Jaroque, Guilherme Nuñez [UNIFESP]; Caseli, Luciano [UNIFESP]; Sartorelli, Patricia [UNIFESP]; http://lattes.cnpq.br/6836392358779448; http://lattes.cnpq.br/8929162910172931; http://lattes.cnpq.br/3306052344968821This work aimed to study the interaction of γ-terpineol with lipid Langmuir monolayers, which served as a model for cell membranes to analyze the possible biological actions of the compound at the molecular level. The phospholipids used to compose the films were dipalmitoylphosphatidylcholine (DPPC), dipalmitoyl phosphatidylethanolamine (DPPE), pure or mixed with cholesterol or with bacterial peptidoglycan. The lipids were spread on the air-water interface through organic solutions assembling a Langmuir monolayer. The γ-terpineol compound was incorporated in the monolayer by co-spreading it with the lipids. The interfacial films formed at the air-water interface were compressed by movable barriers, reaching surface pressures that approached the viscoelastic and thermodynamic properties of a proteolipid bilayer. The interaction of the drug with the monolayers was analyzed using tensiometric measurements (surface pressure- area isotherms, tensiometric stability, hysteresis assays), Brewster angle microscopy, and polarization-modulation infrared reflection-adsorption spectroscopy. The physicochemical properties obtained by these measurements were analyzed, and the interactions of γ-terpineol with the lipids at the air-water interface were inferred and extrapolated for the action of the compound in related cell membranes.