Oral formulation angiotensin-(1-7) therapy attenuates pulmonary and systemic damage in mice with emphysema induced by elastase |
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| Affiliation: | 1. Medical Sciences Faculty of Minas Gerais, Post-Graduate Program in Health Sciences, Minas Gerais, Brazil;2. Department of Physiology and Biophysics, INCT-Nanobiofar, ICB, Federal University of Minas Gerais, Brazil;3. Department of Biological Sciences, Laboratory of Experimental Pathophysiology, Federal University of Ouro Preto, Minas Gerais, Brazil;1. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;2. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;3. Neurosurgery Department, Shiraz University of Medical Sciences, Shiraz, Iran;1. Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, Via Celoria 10, 20133, Milano, Italy;2. Dipartimento di Produzioni Animali, Università degli Studi della Tuscia, Via San Camillo de Lellis, 01100, Viterbo, Italy;1. Department of Medicine - Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States;2. Ina Sue Perlmutter Cystic Fibrosis Laboratory, Children’s Hospital Boston, Harvard Medical School, Boston, MA, United States;1. Dept. of Immunology, Poznan University of Medical Sciences, Rokietnicka 5d St. Poznan, Poland;2. Dept. of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Przybyszewskiego 49 St. Poznan, Poland;1. School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, United States;2. Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, United States;3. Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, United States |
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| Abstract: | Angiotensin-(1-7) [Ang-(1-7)], a peptide of the renin-angiotensin system, has anti-inflammatory, anti-fibrotic and antiproliferative effects in acute or chronic inflammatory disease of respiratory system. In this study, we evaluated the effect of treatment with Ang-(1-7) on pulmonary tissue damage and behavior of mice submitted to experimental model of elastase-induced pulmonary emphysema (PE). Initially, male C57BL/6 mice were randomly assigned into two main groups: control (CTRL) and PE. In the PE group, the animals received three intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals (0.2 IU in 50 μL of saline). The CTRL group received the same volume of saline solution (50 μL). Twenty-four hours after the last instillation, animals of the PE group were randomly divided into two groups: PE and PE + Ang-(1-7). The PE + Ang-(1-7) group was treated with 60 μg/kg of Ang-(1-7) and 92 μg kg of HPβCD in gavage distilled water, 100 μl. The CTRL and PE groups were treated with vehicle (HPβCD- 92 μg/kg in distilled water per gavage, 100 μl), orally daily for 3 weeks. On the 19th day of treatment, all groups were tested in relation to locomotor activity and exploratory behavior. After 48 h, the animals were euthanized and lungs were collected. The animals of PE group presented rupture of alveolar walls and consequently reduction of alveolar tissue area. Treatment with Ang-(1-7) partially restored the alveolar tissue area. The PE reduced the locomotor activity and the exploratory behavior of the mice in relation to the control group. Treatment with Ang-(1-7) attenuated this change. In addition, it was observed that Ang-(1-7) reduced lung levels of IL-1β and increased levels of IL-10. These results show an anti-inflammatory effect of Ang-(1-7), inducing the return of pulmonary homeostasis and attenuation of the behavioral changes in experimental model of PE by elastase. |
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| Keywords: | COPD Pulmonary remodeling Murine model Renin-angiotensin system MAS receptor |
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