Amphibian peptides prevent endotoxemia and bacterial translocation in bile duct-ligated rats

Crit Care Med. 2006 Sep;34(9):2415-20. doi: 10.1097/01.CCM.0000231879.11963.EB.

Abstract

Objective: To investigate the efficacy of amphibian antimicrobial peptides in preventing bacterial translocation and neutralizing endotoxins in bile duct-ligated rats.

Design: Prospective, randomized, controlled animal study.

Setting: Research laboratory in a university hospital.

Subjects: Adult male Wistar rats.

Interventions: Adult male Wistar rats underwent sham operation or bile duct ligation (BDL). Eight groups were studied: sham operation with saline treatment, sham operation with 120 mg/kg tazobactam-piperacillin, sham operation with 2 mg/kg uperin 3.6, sham operation with 2 mg/kg magainin2, BDL with saline treatment, BDL with 120 mg/kg tazobactam-piperacillin, BDL with 2 mg/kg uperin 3.6, and BDL with 2 mg/kg magainin2.

Measurements and main results: Main outcome measures were: endotoxin and tumor necrosis factor-alpha concentrations in plasma and evidence of bacterial translocation in blood, peritoneum, liver, and mesenteric lymph nodes. Endotoxin and tumor necrosis factor-alpha plasma levels were significantly higher in BDL rats compared with sham-operated animals. All amphibian peptides achieved a significant reduction of plasma endotoxin and tumor necrosis factor-alpha concentration when compared with saline- and tazobactam-piperacillin-treated groups. On the other hand, both tazobactam-piperacillin and peptides significantly reduced bacterial growth compared with the control. Tazobactam-piperacillin and magainin2 exerted the maximal inhibition of bacterial growth.

Conclusion: In conclusion, because of their multifunctional properties, amphibian peptides could be interesting compounds to inhibit bacterial translocation and endotoxin release in obstructive jaundice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Amphibian Proteins / pharmacology*
  • Animals
  • Anti-Infective Agents / pharmacology*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacteremia
  • Bacterial Translocation / drug effects*
  • Bile Ducts / surgery
  • Endotoxins / blood
  • Enterococcus faecalis / physiology
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / physiology
  • Jaundice, Obstructive / microbiology*
  • Ligation
  • Liver / microbiology
  • Lymph Nodes / microbiology
  • Magainins
  • Male
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / pharmacology
  • Peptides / pharmacology*
  • Peritoneum / microbiology
  • Piperacillin / pharmacology
  • Prospective Studies
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Tazobactam
  • Tumor Necrosis Factor-alpha / analysis
  • Xenopus Proteins / pharmacology*
  • beta-Lactamase Inhibitors

Substances

  • Amphibian Proteins
  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Endotoxins
  • Enzyme Inhibitors
  • Magainins
  • Peptides
  • Tumor Necrosis Factor-alpha
  • Xenopus Proteins
  • beta-Lactamase Inhibitors
  • uperin 3.6 peptide, Uperoleia mjobergii
  • magainin 2 peptide, Xenopus
  • Penicillanic Acid
  • Tazobactam
  • Piperacillin