Effects of clarithromycin and dexamethasone on mucus production in isografted rat trachea

Pharmacology. 2011;87(1-2):56-62. doi: 10.1159/000322837. Epub 2011 Jan 11.

Abstract

Objectives: The purpose of this study was to develop an animal model for the study of mucus overproduction and to assess the effect of a 14-membered macrolide antibiotic and a glucocorticoid on lipopolysaccharide (LPS)-induced mucus production.

Methods: Tracheas from donor rats were homografted to recipient rats for 4 weeks, and the usefulness of this tracheal homograft model in the study of mucus production was examined.

Results: Oral administration of clarithromycin (CAM) to recipient rats for 4 weeks significantly reduced LPS-induced mucus production in the homografted trachea. Dexamethasone administered for 4 weeks also significantly reduced the mucus volume in LPS-treated homografted trachea compared with that in the control rats. The implanted trachea containing control medium was not histologically different from normal trachea. When the medium instilled into the implanted trachea contained 1 μg/ml LPS, the volume and spinability of mucus produced in the tracheal lumen were significantly increased compared to those in the trachea instilled with control medium. Goblet cell metaplasia was also observed in the implanted trachea containing LPS.

Conclusions: The present study shows that LPS-administered homografted trachea is a good animal model of chronic hypersecretory diseases of the upper and lower airways. CAM and dexamethasone could be treatment choices in such hypersecretory diseases.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use*
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / therapeutic use
  • Clarithromycin / metabolism
  • Clarithromycin / pharmacokinetics
  • Clarithromycin / therapeutic use*
  • Dexamethasone / analogs & derivatives*
  • Dexamethasone / therapeutic use
  • Disease Models, Animal*
  • Glucocorticoids / therapeutic use*
  • Goblet Cells / drug effects
  • Goblet Cells / metabolism
  • Goblet Cells / pathology
  • Lipopolysaccharides / toxicity
  • Male
  • Metaplasia / chemically induced
  • Mucus / chemistry
  • Mucus / metabolism*
  • Rats
  • Rats, Inbred F344
  • Secretory Pathway / drug effects
  • Severity of Illness Index
  • Trachea / drug effects*
  • Trachea / metabolism
  • Trachea / pathology
  • Trachea / transplantation
  • Tracheitis / drug therapy
  • Tracheitis / metabolism
  • Tracheitis / pathology
  • Tracheitis / physiopathology
  • Transplantation, Isogeneic
  • Viscosity

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Lipopolysaccharides
  • dexamethasone 21-phosphate
  • Dexamethasone
  • Clarithromycin