Administration of protegrin peptide IB-367 to prevent endotoxin induced mortality in bile duct ligated rats

A. Giacometti, O. Cirioni, R. Ghiselli, F. Mocchegiani, G. D'Amato, M. Simona Del Prete, F. Orlando, W. Kamysz, J. Lukasiak, V. Saba, G. Scalise

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Postoperative morbidity in patients with obstructive jaundice remains high because of increased susceptibility to endotoxin and the inflammatory cascade. Aims: An experimental study was designed to investigate the efficacy of protegrin peptide IB-367, an antimicrobial positively charged peptide, in neutralising Escherichia coli 0111:B4 lipopolysaccharide (LPS) in bile duct ligated rats. Methods: Adult male Wistar rats were injected intraperitoneally with 2 mg/kg E coli 0111:B4 LPS one 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 IB-367, BDL with placebo, BDL with 120 mg/kg TZP, and BDL with 1 mg/kg IB-367. Results: Main outcome measures were: endotoxin and tumour necrosis factor α (TNF-α) concentrations in plasma, evidence of bacterial translocation in blood and peritoneum, and lethality. After LPS, TNF-α plasma levels were significantly higher in BDL rats compared with sham operated animals. IB-367 caused a significant reduction in plasma endotoxin and TNF-α concentrations compared with placebo and TZP treated groups. In contrast, both TZP and IB- 367 significantly reduced bacterial growth compared with saline treatment. Finally, LPS induced 60% and 55% lethality in BDL placebo and TZP treated rats and no lethality in sham operated rats, while only IB-367 significantly reduced lethality to 10%. Conclusions: By virtue of its dual antimicrobial and antiendotoxin properties, IB-367 could be an interesting compound to inhibit bacterial translocation and endotoxin release in obstructive jaundice.

Original languageEnglish
Pages (from-to)874-878
Number of pages5
JournalGut
Volume52
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

ASJC Scopus subject areas

  • Gastroenterology

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