Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide.
OBJECTIVE
The aim of this study is to investigate whether ambroxol inhibits inflammatory responses in a murine model of lipopolysaccharide-induced acute lung injury (ALI).


METHODS
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.


RESULTS
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).


CONCLUSIONS
Ambroxol inhibited proinflammatory cytokines, reduced lung inflammation and accelerated recovery from LPS-induced ALI.
D000551:Ambroxol / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003907:Dexamethasone / Q000276:immunology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005100:Expectorants / Q000627:therapeutic use*; D007249:Inflammation; D007322:Instillation, Drug; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000032:analysis; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012720:Severity of Illness Index; D012965:Sodium Chloride / Q000276:immunology / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015430:Weight Gain / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D005100:Expectorants; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011506:Proteins; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000551:Ambroxol; D012965:Sodium Chloride; D003907:Dexamethasone