Management of Acute Lung Injury: Palmitoylethanolamide as a New Approach

Int J Mol Sci. 2021 May 24;22(11):5533. doi: 10.3390/ijms22115533.

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and devastating clinical disorders with high mortality and no specific therapy. Lipopolysaccharide (LPS) is usually used intratracheally to induce ALI in mice. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (um-PEA) in mice subjected to LPS-induced ALI. Histopathological analysis reveals that um-PEA reduced alteration in lung after LPS intratracheal administration. Besides, um-PEA decreased wet/dry weight ratio and myeloperoxidase, a marker of neutrophils infiltration, macrophages and total immune cells number and mast cells degranulation in lung. Moreover, um-PEA could also decrease cytokines release of interleukin (IL)-6, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and interleukin (IL)-18. Furthermore, um-PEA significantly inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in ALI, and at the same time decreased extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38/MAPK) expression, that was increased after LPS administration. Our study suggested that um-PEA contrasted LPS-induced ALI, exerting its potential role as an adjuvant anti-inflammatory therapeutic for treating lung injury, maybe also by p38/NF-κB pathway.

Keywords: acute lung injury; cytokines; inflammation; palmitoylethanolamide; ultramicronized.

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology
  • Amides / pharmacology*
  • Amides / therapeutic use
  • Animals
  • Cytokines / metabolism*
  • Ethanolamines / pharmacology*
  • Ethanolamines / therapeutic use
  • Immunohistochemistry
  • Inflammation / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / toxicity
  • MAP Kinase Signaling System / drug effects*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • Mast Cells / drug effects
  • Mast Cells / pathology
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / metabolism
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Palmitic Acids / pharmacology*
  • Palmitic Acids / therapeutic use
  • Peroxidase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Amides
  • Cytokines
  • Ethanolamines
  • IL1B protein, mouse
  • Interleukin-18
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Palmitic Acids
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • NF-KappaB Inhibitor alpha
  • palmidrol
  • Peroxidase
  • JNK Mitogen-Activated Protein Kinases
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases