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Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide

Authors
  • Su, Xiao1
  • Wang, Ling1
  • Song, Yuanlin2
  • Bai, Chunxue1
  • 1 Fudan University, Shanghai, 200032, P. R. China , Shanghai
  • 2 University of California at San Francisco, San Francisco, CA 94143, USA , San Francisco
Type
Published Article
Journal
Intensive Care Medicine
Publisher
Springer-Verlag
Publication Date
Sep 20, 2003
Volume
30
Issue
1
Pages
133–140
Identifiers
DOI: 10.1007/s00134-003-2001-y
Source
Springer Nature
Keywords
License
Yellow

Abstract

ObjectiveThe aim of this study is to investigate whether ambroxol inhibits inflammatory responses in a murine model of lipopolysaccharide-induced acute lung injury (ALI).MethodsMice (n=295) were first intratracheally instilled with lipopolysaccharide (LPS) to induce ALI and then received an intraperitoneal (ip) injection of either normal saline (NS), ambroxol (30 or 90 mg/kg per day) or dexamethasone (2.5 or 5 mg/kg per day) for 7 days. Metabolism (n=10, each), lung morphology (n=5, each) and wet-to-dry lung weight ratio (n=10, each) were studied. The levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and transforming growth factor (TGF-β1)and the protein concentration (n=5 or 7, each) in bronchoalveolar lavage (BAL) were measured.ResultsMice with LPS-induced ALI that were treated with ambroxol at a dosage of 90 mg/kg per day significantly gained weight compared to the control and dexamethasone-treated groups. Ambroxol and dexamethasone significantly reduced the lung hemorrhage, edema, exudation, neutrophil infiltration and total lung injury histology score at 24 and 48 h. In addition, ambroxol and dexamethasone significantly attenuated the lung wet-to-dry weight ratio at 24 and 48 h (p<0.05). Compared to the control group, TNF-α, IL-6 and TGF-β1 levels in the BAL in both ambroxol- and dexamethasone-treated groups were significantly reduced at 24 and 48 h. The protein in BAL, an index of vascular permeability, was also significantly decreased in the ambroxol- and dexamethasone-treated groups (p<0.05).ConclusionAmbroxol inhibited proinflammatory cytokines, reduced lung inflammation and accelerated recovery from LPS-induced ALI.

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