Therapeutic Efficacy of the Polymyxin-like Peptide Ranalexin in an Experimental Model of Endotoxemia

Abstract

Background. A rat model was used to investigate the efficacy of a polycationic peptide, the polymyxin-like ranalexin, in the prevention of lethality in a rat model of septic shock. The effect of ranalexin was compared with those of polymyxin B and imipenem.Methods. Adult male Wistar rats (weight range: 250–300 g) were used for all the experiments. The study included five groups: an uninfected control group C0, an untreated control group C1, and three drug-treated groups that received 1 mg/kg ranalexin (group 2), 20 mg/kg imipenem (group 3), and 3 mg/kg polymyxin B (group 4). Rats, with the exception of the uninfected control group (C0), were given an intraperitoneal injection of 2 × 1010 colony-forming units of Escherichia coli. Each group included 15 animals. Bacterial growth in abdominal exudate and plasma; endotoxin and tumor necrosis factor α (TNF-α) concentrations in plasma, and mortality were evaluated.Results. Results were evaluated 48 h after inoculation. Ranalexin, imipenem, and polymyxin B significantly reduced the lethality (survival was 93.3, 80.0, and 93.3%, respectively) and the growth of E. coli both in abdominal fluid and plasma compared with saline treatment. Ranalexin showed higher antimicrobial activity than polymyxin B and imipenem and, at the same time, exhibited an antiendotoxin activity similar to that of polymyxin B (≤0.015 EU/mL). Finally, ranalexin and polymyxin B significantly reduced plasma TNF-α levels (≤4 pg/mL).Conclusion. Monodose ranalexin treatment prevents bacterial growth, endotoxemia, and mortality in rats with septic shock.