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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Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2022-09, Vol.12 (9), p.1308
Main Authors: Interdonato, Livia, D’amico, Ramona, Cordaro, Marika, Siracusa, Rosalba, Fusco, Roberta, Peritore, Alessio Filippo, Gugliandolo, Enrico, Crupi, Rosalia, Coaccioli, Stefano, Genovese, Tiziana, Impellizzeri, Daniela, Di Paola, Rosanna, Cuzzocrea, Salvatore
Format: Article
Language:English
Subjects:
acute lung injury
Acute respiratory distress syndrome
Adelmidrol
Aerosol therapy
Aerosols
Alveoli
Animal models
Animals
Antioxidants
Azelaic acid
Care and treatment
Chymase
Cytokines
Dosage and administration
Edema
Endothelium
Evaluation
Inflammation
Lipopolysaccharides
Lungs
Mast cells
Membrane permeability
Methods
Morphology
Neutrophils
NF-κB protein
Oxidative stress
Palmitoylethanolamide
Proteins
Respiratory distress syndrome
Trachea
Tryptase
Tumor necrosis factor-TNF
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Summary: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.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom12091308