Atividade anti-inflamatória do cinamato de metila no enfisema pulmonar induzido por elastase em camundongos

Abstract

Pulmonary emphysema is characterized by proteolytic and progressive destruction of the alveolar wall resulting from the inflammatory response and tissue remodeling, which causes loss of the respiratory surface and airflow limitation. Methyl cinnamate (MC) is an ester derivative of cinnamic acid found in several plant species, possessing a wide range of pharmacological effects, including antioxidant and anti-inflammatory actions, however, there are still no records of studies describing its possible therapeutic effects about pulmonar emphysema. In this study, we evaluated the effects of MC on the inflammatory response of the airways and structural changes in the lungs of mice with emphysema induced by elastase, as well as the effects of CM on the activation of airway epithelium in vitro. C57BL/6 mice, of both sexes, received na intratracheal injection of elastase (ELA, 2 IU in 50 μL) or phosphate-saline buffer solution (PBS, control). The treatment ocurred from the 16th to the 20th poststimulus by means of a single daily instillation with MC (1, 10 and 50 μmol/Kg). Twenty-four hours after the last treatment, the inflammatory profile from bronchoalveolar lavage (BAL) and histological changes in the lung were evaluated in the airways and lung. Statistical analyzes were performed with oneway ANOVA, followed by Newman-Kewls post-test. All experimental procedures were approved by CEUA-UFAL nº 85/15. Elastase-stimulated animals exhibited a reduction in body weight from the third day after induction, when compared to control animals. Organs such as spleen, kidney and liver obtained from diferente experimental groups did not show evident morphological changes. Animals with emphysema exhibited intense leukocyte infiltration, characterized by an increase in the count of macrophages, lymphocytes and neutrophils. Treatment with 1, 10 or 50 μmol / Kg of MC reduced the count of all cell types of the inflammatory infiltrate. Histopathological analysis of the lungs of animals with emphysema revealed destruction of the alveolar septa, increased air space and infiltration of inflammatory cells, as well as greater deposition of peribronchiolar collagen, however, all these changes were markedly reduced after treatment with MC, mainly in both higher doses. Treatment with MC reduced the levels of IL-1β and TNF-α in the lung, but not IL-10 levels. These same treatments also decreased the levels of IL-6 in the BAL of emphysematous mice. Cells from the A549 lineage alveolar epithelium, when stimulated in vitro with TNF-α, produced high levels of IL-1β and IL-6, a phenomenon that was inhibited by treatment with MC at concentrations that did not induce cytotoxicity. The production of reactive oxygen species was not affected by treatment with MC. These results demonstrate that CM inhibited airway inflammation and improved induced lung injury, which shows its importance as a candidate for the treatment of pulmonary emphysema.