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

Authors

  • Vanessa Zambelli Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy https://orcid.org/0000-0001-8002-5205
  • Laura Rizzi Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy https://orcid.org/0000-0002-3709-6574
  • Paolo Delvecchio Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy
  • Elena Bresciani Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy https://orcid.org/0000-0002-8247-276X
  • Emanuele Rezoagli Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy https://orcid.org/0000-0002-4506-7212
  • Laura Molteni Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy https://orcid.org/0000-0003-0510-9083
  • Ramona Meanti Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy https://orcid.org/0000-0002-9734-1025
  • Maria Serena Cuttin ASST Vimercate, Vimercate - Italy
  • Giorgio Bovo ASST Vimercate, Vimercate https://orcid.org/0000-0003-1189-6757
  • Silvia Coco Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy
  • Robert J. Omeljaniuk Department of Biology, Lakehead University, Thunder Bay, Ontario - Canada https://orcid.org/0000-0002-8500-6692
  • Vittorio Locatelli Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy
  • Giacomo Bellani Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy https://orcid.org/0000-0002-3089-205X
  • Antonio Torsello Department of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy

DOI:

https://doi.org/10.33393/dti.2021.2347

Keywords:

ARDS, GHS , Hexarelin, Inflammation, Lung fibrosis

Abstract

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.

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References

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Published

2021-11-21

How to Cite

Zambelli, V., Rizzi, L., Delvecchio, P., Bresciani, E., Rezoagli, E. ., Molteni, L., Meanti, R., Cuttin, M. S., Bovo, G., Coco, S., Omeljaniuk , R. . J., Locatelli, V., Bellani, G., & Torsello, A. (2021). Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury. Drug Target Insights, 15(1), 26–33. https://doi.org/10.33393/dti.2021.2347

Issue

Section

Original Research Article
Received 2021-10-05
Accepted 2021-11-15
Published 2021-11-21

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