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Effects of the antimicrobial peptide BMAP-27 in a mouse model of obstructive jaundice stimulated by lipopolysaccharide.

Abstract
An experimental study was designed to investigate the efficacy of BMAP-27, a compound of the cathelicidin family, in neutralizing Escherichia coli 0111:B4 lipopolysaccharide (LPS) in bile duct-ligated mice. Main outcome measures were: endotoxin and TNF-alpha concentrations in plasma, evidence of bacterial translocation in blood and peritoneum, and lethality. Adult male BALB/c mice were injected intraperitoneally with 2 mg/kg E. coli 0111:B4 LPS 1 week after sham operation or bile duct ligation (BDL). Six groups were studied: sham with placebo, sham with 120 mg/kg tazobactam-piperacillin (TZP), sham with 1 mg/kg BMAP-27, BDL with placebo, BDL with 120 mg/kg TZP, and BDL with 1mg/kg BMAP-27. After LPS, TNF-alpha plasma levels were significantly higher in BDL mice compared to sham-operated animals. BMAP-27 achieved a significant reduction of plasma endotoxin and TNF-alpha concentration when compared with placebo- and TZP-treated groups. On the other hand, both TZP and BMAP-27 significantly reduced the bacterial growth compared with saline treatment. Finally, LPS induced 60% and 55% lethality in BDL placebo- and TZP-treated treated mice and no lethality in sham-operated mice, while only BMAP-27 significantly reduced the lethality to 10%. In light of its dual antimicrobial and anti-endotoxin properties, BMAP-27 could be an interesting compound to inhibit bacterial translocation and endotoxin release in obstructive jaundice.
AuthorsRoberto Ghiselli, Oscar Cirioni, Andrea Giacometti, Federico Mocchegiani, Fiorenza Orlando, Cristina Bergnach, Barbara Skerlavaj, Carmela Silvestri, Agnese Della Vittoria, Margherita Zanetti, Marco Rocchi, Giorgio Scalise, Vittorio Saba
JournalPeptides (Peptides) Vol. 27 Issue 11 Pg. 2592-9 (Nov 2006) ISSN: 0196-9781 [Print] United States
PMID16806583 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antimicrobial Cationic Peptides
  • BMAP-27
  • Lipopolysaccharides
  • Proteins
  • Tumor Necrosis Factor-alpha
Topics
  • Animals
  • Antimicrobial Cationic Peptides (therapeutic use)
  • Bacterial Translocation (drug effects)
  • Disease Models, Animal
  • Jaundice, Obstructive (chemically induced, drug therapy)
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Proteins (metabolism, therapeutic use)
  • Tumor Necrosis Factor-alpha (blood)

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