Logo image
Back
Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide
Journal article   Open access   Peer reviewed

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

Xiao Su, Ling Wang, Yuanlin Song and Chunxue Bai
Intensive care medicine, Vol.30(1), pp.133-140
01/2004
DOI: 10.1007/s00134-003-2001-y
PMCID: PMC8227363
PMID: 14504727
url
https://doi.org/10.1007/s00134-003-2001-yView
Published (Version of record) Open Access

Abstract

The aim of this study is to investigate whether ambroxol inhibits inflammatory responses in a murine model of lipopolysaccharide-induced acute lung injury (ALI). Mice (n=295) were first intratracheally instilled with lipopolysaccharide (LPS) to induce ALI and then received an intraperitoneal (i.p.) 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-alpha), interleukin-6 (IL-6) and transforming growth factor (TGF-beta1) and the protein concentration (n=5 or 7, each) in bronchoalveolar lavage (BAL) were measured. Mice 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-alpha, IL-6 and TGF-beta1 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). Ambroxol inhibited proinflammatory cytokines, reduced lung inflammation and accelerated recovery from LPS-induced ALI.
 Inflammation Ambroxol - immunology Ambroxol - therapeutic use Animals Anti-Inflammatory Agents - immunology Anti-Inflammatory Agents - therapeutic use Bronchoalveolar Lavage Fluid - cytology Bronchoalveolar Lavage Fluid - immunology Dexamethasone - immunology Dexamethasone - therapeutic use Disease Models, Animal Drug Administration Schedule Drug Evaluation, Preclinical Expectorants - therapeutic use Instillation, Drug Interleukin-6 - analysis Lipopolysaccharides Mice Organ Size - drug effects Proteins - analysis Respiratory Distress Syndrome - drug therapy Respiratory Distress Syndrome - immunology Respiratory Distress Syndrome - microbiology Respiratory Distress Syndrome - pathology Severity of Illness Index Sodium Chloride - immunology Sodium Chloride - therapeutic use Transforming Growth Factor beta - analysis Transforming Growth Factor beta1 Tumor Necrosis Factor-alpha - analysis Weight Gain - drug effects

Details

Metrics

11 Record Views
116 Times Cited - Web of Science
Logo image