Protective effect of citropin 1.1 and tazobactam-piperacillin against oxidative damage and lethality in mice models of gram-negative sepsis.
BACKGROUND
Gram-negative sepsis ranks as the leading cause of death in intensive care units, and its incidence is increasing steadily and mortality rates has not changed much over recent decades.


METHODS
We investigated the efficacy of the amphibian peptide, citropin 1.1 alone and in combination with tazobactam-piperacillin (TZP) in two experimental mice models of gram-negative sepsis. Animals were given an intraperitoneal injection of (1) 1 mg Escherichia coli 0111:B4 LPS, and (2) 2×10(10) CFU of E. coli ATCC 25922. For each model, all animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/Kg citropin 1.1 and 120 mg/Kg of TZP, and finally 1 mg/Kg citropin 1.1 plus 60 mg/Kg of TZP. Lethality, bacterial growth in blood and peritoneum, and oxidative stress indices in plasma were evaluated.


RESULTS
All compounds reduced the lethality compared with controls. Treatment with citropin 1.1 resulted in significant decrease in plasma endotoxin and cytokine levels, while TZP exerted opposed effect. The combination between citropin 1.1 and TZP proved to be the most effective treatment in reducing all variables measured.


CONCLUSIONS
Due to its multifunctional properties, citropin 1.1 may become an important future consideration to treat conditions in which oxidative organ failure may be present.
Ghiselli
Roberto
R
General Surgery and Surgery Methodology Clinic, Università Politecnica delle Marche, and Analysis Laboratory, Ospedali Riuniti Umberto I-Lancisi-Salesi, Ancona, Italy.
Silvestri
Carmela
C
Cirioni
Oscar
O
Kamysz
Wojciech
W
Orlando
Fiorenza
F
Calcinari
Alessandra
A
Kamysz
Elzbieta
E
Casteletti
Sefora
S
Rimini
Massimiliano
M
Tocchini
Massimo
M
Giacometti
Andrea
A
Guerrieri
Mario
M
D029845:Amphibian Proteins / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000145:classification / Q000187:drug effects* / Q000254:growth & development; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology*; D000078142:Tazobactam
D029845:Amphibian Proteins; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C121829:citropin 1.1 protein, Litoria; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin