S-thanatin enhances the efficacy of tigecycline in an experimental rat model of polymicrobial peritonitis.
We investigated the efficacy of the peptide s-thanatin alone and in combination with tigecycline in an animal model of sepsis induced by cecal ligation and puncture. Adult male Wistar rats were randomized to receive intravenously isotonic sodium chloride solution, 5mg/kg s-thanatin, 2mg/kg tigecycline, 5mg/kg s-thanatin combined with 2mg/kg tigecycline. The experiment was also performed with administration of the drugs 360 min after the surgical procedure to better investigate the clinical situation where there is an interval between the onset of sepsis and the initiation of therapy. Lethality, bacterial growth in blood, peritoneum, spleen and liver, and NO indices were evaluated. All compounds reduced the lethality when compared to control. In all experiments, the compounds reduced significantly bacterial growth and lethality compared with saline treatment. Treatment with s-thanatin resulted in significant decrease in plasma NO levels compared to tigecycline and control group. The combination between s-thanatin and tigecycline proved to be the most effective treatment in reducing all variables measured. S-thanatin may have potential therapeutic usefulness alone and when associated to tigecycline in polymicrobial peritonitis.
Cirioni
Oscar
O
Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
Wu
Guoqiu
G
Li
Linxian
L
Orlando
Fiorenza
F
Silvestri
Carmela
C
Ghiselli
Roberto
R
Shen
Zilong
Z
Scalise
Alessandro
A
Gabrielli
Eleonora
E
Scuppa
Daniele
D
Romiti
Chiara
C
Provinciali
Mauro
M
Guerrieri
Mario
M
Giacometti
Andrea
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D008911:Minocycline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D023421:Models, Animal; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar; D000078304:Tigecycline; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C098076:thanatin; D000078304:Tigecycline; D008911:Minocycline