TY - JOUR
T1 - S-thanatin enhances the efficacy of tigecycline in an experimental rat model of polymicrobial peritonitis
AU - Cirioni, Oscar
AU - Wu, Guoqiu
AU - Li, Linxian
AU - Orlando, Fiorenza
AU - Silvestri, Carmela
AU - Ghiselli, Roberto
AU - Shen, Zilong
AU - Scalise, Alessandro
AU - Gabrielli, Eleonora
AU - Scuppa, Daniele
AU - Romiti, Chiara
AU - Provinciali, Mauro
AU - Guerrieri, Mario
AU - Giacometti, Andrea
PY - 2010/7
Y1 - 2010/7
N2 - 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, 5 mg/kg s-thanatin, 2 mg/kg tigecycline, 5 mg/kg s-thanatin combined with 2 mg/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.
AB - 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, 5 mg/kg s-thanatin, 2 mg/kg tigecycline, 5 mg/kg s-thanatin combined with 2 mg/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.
KW - Antimicrobial peptides
KW - Polymicrobial peritonitis
KW - S-thanatin
KW - Tigecycline
UR - http://www.scopus.com/inward/record.url?scp=77952549104&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952549104&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2010.03.034
DO - 10.1016/j.peptides.2010.03.034
M3 - Article
C2 - 20381561
AN - SCOPUS:77952549104
VL - 31
SP - 1231
EP - 1236
JO - Peptides
JF - Peptides
SN - 0196-9781
IS - 7
ER -