Liraglutide attenuates lipopolysaccharide-induced acute lung injury in mice

Eur J Pharmacol. 2016 Nov 15:791:735-740. doi: 10.1016/j.ejphar.2016.10.016. Epub 2016 Oct 15.

Abstract

Liraglutide, an effective drug for the treatment of diabetes, has been proven to demonstrate anti-inflammatory and immunomodulatory effects. Hence, this study explored the effects and mechanism of action of liraglutide on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Male BALB/c mice were pre-conditioned with liraglutide or saline prior to intraperitoneal LPS or saline administration. Histopathological examination of lung, the wet/dry (W/D)weight ratio, protein content, inflammatory cell numbers and pro-inflammatory cytokine levels in broncho-alveolar lavage fluid (BAL fluid) were conducted. The effects of liraglutide on the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome signalling pathway were assessed by Western blot. Pre-treatment with liraglutide decreased the wet-to-dry weight ratio and protein concentrations in BAL fluid and neutrophil infiltration in the lung tissues. Liraglutide also significantly reduced the interleukin-1β and interleukin-18 levels in BAL fluid, as well as effectively inhibited the expression of NLRP3 inflammasome. These results indicated that liraglutide pre-treatment attenuated LPS-induced ALI by inhibiting the NLRP3 inflammasome pathway.

Keywords: Acute lung injury; Inflammation; Lipopolysaccharide; Liraglutide; NLRP3 inflammasome.

MeSH terms

  • Acute Lung Injury / chemically induced*
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Gene Expression Regulation / drug effects
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / pharmacology*
  • Liraglutide / pharmacology*
  • Liraglutide / therapeutic use
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Organ Size / drug effects

Substances

  • Interleukin-18
  • Interleukin-1beta
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Liraglutide