Protective effect of erdosteine against hypochlorous acid-induced acute lung injury and lipopolysaccharide-induced neutrophilic lung inflammation in mice.
The effect of erdosteine, a mucoactive drug, on hypochlorous acid (HOCl)-induced lung injury, and the lipopolysaccharide (LPS)-induced increase in tumour necrosis factor-alpha (TNF-alpha) production and neutrophil recruitment into the airway, was investigated. Male BALB/c mice were orally administered erdosteine (3-100 mgkg(-1)), ambroxol hydrochloride (ambroxol) (3-30 mgkg(-1)), S-carboxymethyl-L-cysteine (S-CMC) (100-600 mgkg(-1)) or prednisolone (10 mgkg(-1)), 1 h before intratracheal injection of HOCl or LPS. In the HOCl-injected mice, erdosteine markedly suppressed increases in the ratios of lung wet weight to bodyweight and lung dry weight to bodyweight, whereas the other mucoactive drugs ambroxol and S-CMC had little effect. Erdosteine also inhibited the LPS-induced neutrophil influx, although it did not affect the increased level of TNF-alpha in the bronchoalveolar lavage fluid. The results suggest that attenuation of reactive oxygen species and neutrophil recruitment is involved in the clinical efficacy of erdosteine in the treatment of chronic bronchitis.
Hayashi
K
K
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd, Shizuoka, Japan.
Hosoe
H
H
Kaise
T
T
Ohmori
K
K
D000284:Administration, Oral; D000818:Animals; D001991:Bronchitis / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002908:Chronic Disease; D004195:Disease Models, Animal; D005100:Expectorants / Q000494:pharmacology*; D006997:Hypochlorous Acid / Q000008:administration & dosage / Q000009:adverse effects; D007249:Inflammation; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017382:Reactive Oxygen Species; D013864:Thioglycolates / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D005100:Expectorants; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D013864:Thioglycolates; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; D006997:Hypochlorous Acid; C048498:erdosteine