Effects of the antimicrobial peptide BMAP-27 in a mouse model of obstructive jaundice stimulated by lipopolysaccharide.
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.
Ghiselli
Roberto
R
Department of General Surgery, I.N.R.C.A. I.R.R.C.S., Università Politecnica delle Marche, Ancona, Italy.
Cirioni
Oscar
O
Giacometti
Andrea
A
Mocchegiani
Federico
F
Orlando
Fiorenza
F
Bergnach
Cristina
C
Skerlavaj
Barbara
B
Silvestri
Carmela
C
Vittoria
Agnese Della
AD
Zanetti
Margherita
M
Rocchi
Marco
M
Scalise
Giorgio
G
Saba
Vittorio
V
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D018988:Bacterial Translocation / Q000187:drug effects; D004195:Disease Models, Animal; D041781:Jaundice, Obstructive / Q000139:chemically induced / Q000188:drug therapy*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000378:metabolism / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D023181:Antimicrobial Cationic Peptides; C102359:BMAP-27; D008070:Lipopolysaccharides; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha