Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury

Introduction: Acute respiratory distress syndrome (ARDS) is an acute form of diffuse lung injury characterized by (i) an intense inflammatory response, (ii) increased pulmonary vascular permeability, and (iii) the loss of respiratory pulmonary tissue. In this article we explore the therapeutic poten...

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Autores principales:	Vanessa Zambelli, Laura Rizzi, Paolo Delvecchio, Elena Bresciani, Emanuele Rezoagli, Laura Molteni, Ramona Meanti, Maria Serena Cuttin, Giorgio Bovo, Silvia Coco, Robert J. Omeljaniuk, Vittorio Locatelli, Giacomo Bellani, Antonio Torsello
Formato:	article
Lenguaje:	EN
Publicado:	AboutScience Srl 2021
Materias:	ARDS GHS Hexarelin Inflammation Lung fibrosis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/f5754c4dc3724904a0ebe58d6f7c1008
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spelling	oai:doaj.org-article:f5754c4dc3724904a0ebe58d6f7c10082021-11-29T09:17:20ZHexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury10.33393/dti.2021.23471177-3928https://doaj.org/article/f5754c4dc3724904a0ebe58d6f7c10082021-11-01T00:00:00Zhttps://journals.aboutscience.eu/index.php/dti/article/view/2347https://doaj.org/toc/1177-3928Introduction: Acute respiratory distress syndrome (ARDS) is an acute form of diffuse lung injury characterized by (i) an intense inflammatory response, (ii) increased pulmonary vascular permeability, and (iii) the loss of respiratory pulmonary tissue. In this article we explore the therapeutic potential of hexarelin, a synthetic hexapeptide growth hormone secretagogue (GHS), in an experimental model of ARDS. Hexarelin has anti-inflammatory properties and demonstrates cardiovascular-protective activities including the inhibition of cardiomyocyte apoptosis and cardiac fibrosis, both of which may involve the angiotensin-converting enzyme (ACE) system. Methods: In our experimental model, ARDS was induced by the instillation of 100 mM HCl into the right bronchus; these mice were treated with hexarelin (320 μg/kg, ip) before (Pre) or after (Post) HCl challenge, or with vehicle. Respiratory system compliance, blood gas analysis, and differential cell counts in a selective bronchoalveolar lavage (BAL) were determined 6 or 24 hours after HCl instillation. In an extended study, mice were observed for a subsequent 14 days in order to assess lung fibrosis. Results: Hexarelin induced a significant improvement in lung compliance and a reduction of the number of total immune cells in BAL 24 hours after HCl instillation, accompanied with a lower recruitment of neutrophils compared with the vehicle group. At day 14, hexarelin-treated mice presented with less pulmonary collagen deposition compared with vehicle-treated controls. Conclusions: Our data suggest that hexarelin can inhibit the early phase of the inflammatory response in a murine model of HCl-induced ARDS, thereby blunting lung remodeling processes and fibrotic development. Vanessa ZambelliLaura RizziPaolo DelvecchioElena BrescianiEmanuele RezoagliLaura MolteniRamona MeantiMaria Serena CuttinGiorgio BovoSilvia CocoRobert J. Omeljaniuk Vittorio LocatelliGiacomo BellaniAntonio TorselloAboutScience SrlarticleARDSGHS HexarelinInflammationLung fibrosisTherapeutics. PharmacologyRM1-950ENDrug Target Insights, Vol 15, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ARDS GHS Hexarelin Inflammation Lung fibrosis Therapeutics. Pharmacology RM1-950
spellingShingle	ARDS GHS Hexarelin Inflammation Lung fibrosis Therapeutics. Pharmacology RM1-950 Vanessa Zambelli Laura Rizzi Paolo Delvecchio Elena Bresciani Emanuele Rezoagli Laura Molteni Ramona Meanti Maria Serena Cuttin Giorgio Bovo Silvia Coco Robert J. Omeljaniuk Vittorio Locatelli Giacomo Bellani Antonio Torsello Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury
description	Introduction: Acute respiratory distress syndrome (ARDS) is an acute form of diffuse lung injury characterized by (i) an intense inflammatory response, (ii) increased pulmonary vascular permeability, and (iii) the loss of respiratory pulmonary tissue. In this article we explore the therapeutic potential of hexarelin, a synthetic hexapeptide growth hormone secretagogue (GHS), in an experimental model of ARDS. Hexarelin has anti-inflammatory properties and demonstrates cardiovascular-protective activities including the inhibition of cardiomyocyte apoptosis and cardiac fibrosis, both of which may involve the angiotensin-converting enzyme (ACE) system. Methods: In our experimental model, ARDS was induced by the instillation of 100 mM HCl into the right bronchus; these mice were treated with hexarelin (320 μg/kg, ip) before (Pre) or after (Post) HCl challenge, or with vehicle. Respiratory system compliance, blood gas analysis, and differential cell counts in a selective bronchoalveolar lavage (BAL) were determined 6 or 24 hours after HCl instillation. In an extended study, mice were observed for a subsequent 14 days in order to assess lung fibrosis. Results: Hexarelin induced a significant improvement in lung compliance and a reduction of the number of total immune cells in BAL 24 hours after HCl instillation, accompanied with a lower recruitment of neutrophils compared with the vehicle group. At day 14, hexarelin-treated mice presented with less pulmonary collagen deposition compared with vehicle-treated controls. Conclusions: Our data suggest that hexarelin can inhibit the early phase of the inflammatory response in a murine model of HCl-induced ARDS, thereby blunting lung remodeling processes and fibrotic development.
format	article
author	Vanessa Zambelli Laura Rizzi Paolo Delvecchio Elena Bresciani Emanuele Rezoagli Laura Molteni Ramona Meanti Maria Serena Cuttin Giorgio Bovo Silvia Coco Robert J. Omeljaniuk Vittorio Locatelli Giacomo Bellani Antonio Torsello
author_facet	Vanessa Zambelli Laura Rizzi Paolo Delvecchio Elena Bresciani Emanuele Rezoagli Laura Molteni Ramona Meanti Maria Serena Cuttin Giorgio Bovo Silvia Coco Robert J. Omeljaniuk Vittorio Locatelli Giacomo Bellani Antonio Torsello
author_sort	Vanessa Zambelli
title	Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury
title_short	Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury
title_full	Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury
title_fullStr	Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury
title_full_unstemmed	Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury
title_sort	hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury
publisher	AboutScience Srl
publishDate	2021
url	https://doaj.org/article/f5754c4dc3724904a0ebe58d6f7c1008
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Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury

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