Amphibian peptides prevent endotoxemia and bacterial translocation in bile duct-ligated rats.
OBJECTIVE
To investigate the efficacy of amphibian antimicrobial peptides in preventing bacterial translocation and neutralizing endotoxins in bile duct-ligated rats.


METHODS
Prospective, randomized, controlled animal study.


METHODS
Research laboratory in a university hospital.


METHODS
Adult male Wistar rats.


METHODS
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.


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.


CONCLUSIONS
In conclusion, because of their multifunctional properties, amphibian peptides could be interesting compounds to inhibit bacterial translocation and endotoxin release in obstructive jaundice.
Giacometti
Andrea
A
Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
Cirioni
Oscar
O
Ghiselli
Roberto
R
Mocchegiani
Federico
F
Silvestri
Carmela
C
Orlando
Fiorenza
F
Kamysz
Wojciech
W
Licci
Alberto
A
Kamysz
Elzbieta
E
Lukasiak
Jerzy
J
Saba
Vittorio
V
Scalise
Giorgio
G
D029845:Amphibian Proteins / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D016470:Bacteremia; D018988:Bacterial Translocation / Q000187:drug effects*; D001652:Bile Ducts / Q000601:surgery; D004731:Endotoxins / Q000097:blood; D013293:Enterococcus faecalis / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000502:physiology; D041781:Jaundice, Obstructive / Q000382:microbiology*; D008026:Ligation; D008099:Liver / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D054806:Magainins; D008297:Male; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010537:Peritoneum / Q000382:microbiology; D010878:Piperacillin / Q000494:pharmacology; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000078142:Tazobactam; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D029867:Xenopus Proteins / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors
D029845:Amphibian Proteins; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004731:Endotoxins; D004791:Enzyme Inhibitors; D054806:Magainins; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D029867:Xenopus Proteins; D065093:beta-Lactamase Inhibitors; C121472:uperin 3.6 peptide, Uperoleia mjobergii; C053301:magainin 2 peptide, Xenopus; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin