Aerosol-Administered Adelmidrol Attenuates Lung Inflammation in a Murine Model of Acute Lung Injury

Acute lung injury (ALI) is a common and devastating clinical disorder with a high mortality rate and no specific therapy. The pathophysiology of ALI is characterized by increased alveolar/capillary permeability, lung inflammation, oxidative stress and structural damage to lung tissues, which can pro...

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Main Authors: Livia Interdonato, Ramona D’amico, Marika Cordaro, Rosalba Siracusa, Roberta Fusco, Alessio Filippo Peritore, Enrico Gugliandolo, Rosalia Crupi, Stefano Coaccioli, Tiziana Genovese, Daniela Impellizzeri, Rosanna Di Paola, Salvatore Cuzzocrea
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/12/9/1308
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author Livia Interdonato
Ramona D’amico
Marika Cordaro
Rosalba Siracusa
Roberta Fusco
Alessio Filippo Peritore
Enrico Gugliandolo
Rosalia Crupi
Stefano Coaccioli
Tiziana Genovese
Daniela Impellizzeri
Rosanna Di Paola
Salvatore Cuzzocrea
author_facet Livia Interdonato
Ramona D’amico
Marika Cordaro
Rosalba Siracusa
Roberta Fusco
Alessio Filippo Peritore
Enrico Gugliandolo
Rosalia Crupi
Stefano Coaccioli
Tiziana Genovese
Daniela Impellizzeri
Rosanna Di Paola
Salvatore Cuzzocrea
author_sort Livia Interdonato
collection DOAJ
description Acute lung injury (ALI) is a common and devastating clinical disorder with a high mortality rate and no specific therapy. The pathophysiology of ALI is characterized by increased alveolar/capillary permeability, lung inflammation, oxidative stress and structural damage to lung tissues, which can progress to acute respiratory distress syndrome (ARDS). Adelmidrol (ADM), an analogue of palmitoylethanolamide (PEA), is known for its anti-inflammatory and antioxidant functions, which are mainly due to down-modulating mast cells (MCs) and promoting endogenous antioxidant defense. The aim of this study is to evaluate the protective effects of ADM in a mice model of ALI, induced by intratracheal administration of lipopolysaccharide (LPS) at the dose of 5 mg/kg. ADM 2% was administered by aerosol 1 and 6 h after LPS instillation. In this study, we clearly demonstrated that ADM reduced lung damage and airway infiltration induced by LPS instillation. At the same time, ADM counteracted the increase in MC number and the expression of specific markers of MC activation, i.e., chymase and tryptase. Moreover, ADM reduced oxidative stress by upregulating antioxidant enzymes as well as modulating the Nf-kB pathway and the resulting pro-inflammatory cytokine release. These results suggest that ADM could be a potential candidate in the management of ALI.
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spelling doaj.art-71fbf0437602446faf093237e217156e2023-11-23T15:16:32ZengMDPI AGBiomolecules2218-273X2022-09-01129130810.3390/biom12091308Aerosol-Administered Adelmidrol Attenuates Lung Inflammation in a Murine Model of Acute Lung InjuryLivia Interdonato0Ramona D’amico1Marika Cordaro2Rosalba Siracusa3Roberta Fusco4Alessio Filippo Peritore5Enrico Gugliandolo6Rosalia Crupi7Stefano Coaccioli8Tiziana Genovese9Daniela Impellizzeri10Rosanna Di Paola11Salvatore Cuzzocrea12Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Veterinary Science, University of Messina, 98168 Messina, ItalyDepartment of Veterinary Science, University of Messina, 98168 Messina, ItalyGeneral Medical Clinic and Medical Therapy, Rheumatology and Medical Therapy of the Pain, University of Perugia, “Polo di Terni”, “AO Santa Maria” of Terni, 06129 Perugia, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Veterinary Science, University of Messina, 98168 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyAcute lung injury (ALI) is a common and devastating clinical disorder with a high mortality rate and no specific therapy. The pathophysiology of ALI is characterized by increased alveolar/capillary permeability, lung inflammation, oxidative stress and structural damage to lung tissues, which can progress to acute respiratory distress syndrome (ARDS). Adelmidrol (ADM), an analogue of palmitoylethanolamide (PEA), is known for its anti-inflammatory and antioxidant functions, which are mainly due to down-modulating mast cells (MCs) and promoting endogenous antioxidant defense. The aim of this study is to evaluate the protective effects of ADM in a mice model of ALI, induced by intratracheal administration of lipopolysaccharide (LPS) at the dose of 5 mg/kg. ADM 2% was administered by aerosol 1 and 6 h after LPS instillation. In this study, we clearly demonstrated that ADM reduced lung damage and airway infiltration induced by LPS instillation. At the same time, ADM counteracted the increase in MC number and the expression of specific markers of MC activation, i.e., chymase and tryptase. Moreover, ADM reduced oxidative stress by upregulating antioxidant enzymes as well as modulating the Nf-kB pathway and the resulting pro-inflammatory cytokine release. These results suggest that ADM could be a potential candidate in the management of ALI.https://www.mdpi.com/2218-273X/12/9/1308acute lung injuryAdelmidrolmast cellsinflammationoxidative stress
spellingShingle Livia Interdonato
Ramona D’amico
Marika Cordaro
Rosalba Siracusa
Roberta Fusco
Alessio Filippo Peritore
Enrico Gugliandolo
Rosalia Crupi
Stefano Coaccioli
Tiziana Genovese
Daniela Impellizzeri
Rosanna Di Paola
Salvatore Cuzzocrea
Aerosol-Administered Adelmidrol Attenuates Lung Inflammation in a Murine Model of Acute Lung Injury
Biomolecules
acute lung injury
Adelmidrol
mast cells
inflammation
oxidative stress
title Aerosol-Administered Adelmidrol Attenuates Lung Inflammation in a Murine Model of Acute Lung Injury
title_full Aerosol-Administered Adelmidrol Attenuates Lung Inflammation in a Murine Model of Acute Lung Injury
title_fullStr Aerosol-Administered Adelmidrol Attenuates Lung Inflammation in a Murine Model of Acute Lung Injury
title_full_unstemmed Aerosol-Administered Adelmidrol Attenuates Lung Inflammation in a Murine Model of Acute Lung Injury
title_short Aerosol-Administered Adelmidrol Attenuates Lung Inflammation in a Murine Model of Acute Lung Injury
title_sort aerosol administered adelmidrol attenuates lung inflammation in a murine model of acute lung injury
topic acute lung injury
Adelmidrol
mast cells
inflammation
oxidative stress
url https://www.mdpi.com/2218-273X/12/9/1308
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