Therapeutic efficacy of the polymyxin-like peptide ranalexin in an experimental model of endotoxemia.
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 C(0), an untreated control group C(1), 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 (C(0)), were given an intraperitoneal injection of 2 x 10(10) colony-forming units of Escherichia coli. Each group included 15 animals. Bacterial growth in abdominal exudate and plasma; endotoxin and tumor necrosis factor alpha (TNF-alpha) 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 (< or =0.015 EU/mL). Finally, ranalexin and polymyxin B significantly reduced plasma TNF-alpha levels (< or =4 pg/mL).


CONCLUSIONS
Monodose ranalexin treatment prevents bacterial growth, endotoxemia, and mortality in rats with septic shock.
Ghiselli
R
R
Department of General Surgery, INRCA IRRCS, University of Ancona, 60020 Torrette di Ancona, Italy.
Giacometti
A
A
Cirioni
O
O
Orlando
F
F
Mocchegiani
F
F
Pacci
A M
AM
Scalise
G
G
Saba
V
V
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000188:drug therapy* / Q000401:mortality; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000401:mortality; D015378:Imipenem / Q000494:pharmacology; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011112:Polymyxin B / Q000494:pharmacology; D011113:Polymyxins; D051381:Rats; D015996:Survival Rate; D013845:Thienamycins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010456:Peptides, Cyclic; D011113:Polymyxins; D013845:Thienamycins; D014409:Tumor Necrosis Factor-alpha; C086618:ranalexin; D015378:Imipenem; D011112:Polymyxin B