Protective effect of citropin 1.1 and tazobactam-piperacillin against oxidative damage and lethality in mice models of gram-negative sepsis

Abstract

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.

Materials and 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.

Conclusion: 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.