antimicrobial-peptide-ib-367 and Escherichia-coli-Infections

Postoperative morbidity in patients with obstructive jaundice remains high because of increased susceptibility to endotoxin and the inflammatory cascade.. 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.. 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.. Main outcome measures were: endotoxin and tumour necrosis factor alpha (TNF-alpha) concentrations in plasma, evidence of bacterial translocation in blood and peritoneum, and lethality. After LPS, TNF-alpha plasma levels were significantly higher in BDL rats compared with sham operated animals. IB-367 caused a significant reduction in plasma endotoxin and TNF-alpha 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%.. 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.

Topics: Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Bacterial Translocation; Bile Ducts; Cholestasis; Disease Models, Animal; Endotoxemia; Escherichia coli Infections; Ligation; Lipopolysaccharides; Male; Peptides; Postoperative Complications; Proteins; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The therapeutic efficacy of protegrin peptide IB-367 was investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 1mg Escherichia coli 0111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 X 10(10) CFU of E. coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1mg/kg of IB-367, 60mg/kg piperacillin and 1mg/kg of IB-367 plus 60mg/kg piperacillin. The peptide demonstrated lower level of antimicrobial activity than piperacillin, nevertheless it exhibited the dual properties of antimicrobial and antiendotoxin agent. Finally IB-367 and piperacillin association showed to be the most effective therapeutic approach.

Topics: Animals; Antimicrobial Cationic Peptides; Cecum; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli Infections; Ligation; Lipopolysaccharides; Male; Microbial Sensitivity Tests; Peptides; Peritonitis; Piperacillin; Proteins; Punctures; Rats; Rats, Wistar; Shock, Septic