Effect of azithromycin on acute inflammatory lesions and colonic bacterial load in a murine model of experimental colitis

Dig Dis Sci. 2010 Aug;55(8):2211-8. doi: 10.1007/s10620-009-1034-7. Epub 2009 Nov 19.

Abstract

Background: The aim of this study was to investigate the effect of the macrolide antibiotic azithromycin on mucosal changes and colonic bacterial load in a murine model of colitis.

Methods: Colitis was induced in CD1 mice using enema of 0.2% solution of dinitrofluorobenzene, combined with skin sensitization. Four experimental groups of animals (N = 10 per group) were treated with 50 mg/kg/day azithromycin (AZ) or metronidazole (MN) perorally, starting 24 h before (AZ-1, MN-1) or 6 h after (AZ+1, MN+1) induction of colitis and for consecutive 5 days. Additional experimental mice group was treated with 10 mg/kg/day methylprednisolone intraperitoneally after induction of experimental colitis in the same manner (MP). Two control groups consisted of healthy animals (C) that received the challenge enema with phosphate-buffered saline (PBS) and animals with experimental colitis (chall) treated with equivolume of PBS perorally. Clinical score (0-5) and histopathologic score (0-30) were used to assess inflammatory changes, and colon washings were used to determine changes in bacterial load.

Results: The anti-inflammatory effect of azithromycin did not differ from the effect of methylprednisolone, when compared with control group with experimental colitis. Metronidazole did not show a significant anti-inflammatory effect. Number of colonic bacteria did not differ significantly between control and experimental groups of animals.

Conclusions: We documented the anti-inflammatory effect of azithromycin in a murine model of acute colitis, suggesting that effects were targeted to oxidative burst and on mucosal/bacterial interface, independent of luminal bacterial load. Further studies should be focused on effect of azithromycin on the role of bacterial biofilm in perpetuation of chronic intestinal inflammation.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Azithromycin / administration & dosage
  • Azithromycin / therapeutic use*
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colon / microbiology*
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Male
  • Methylprednisolone / therapeutic use
  • Metronidazole / therapeutic use
  • Mice
  • Specific Pathogen-Free Organisms

Substances

  • Anti-Bacterial Agents
  • Metronidazole
  • Azithromycin
  • Methylprednisolone