Protective effects of antimicrobial peptide S-thanatin against endotoxic shock in mice introduced by LPS

Sepsis continues to be a major unresolved medical challenge of the present. Severe sepsis and septic shock are the leading causes of multiple organ failure and mortality in noncoronary intensive care units (ICUs). The primary reason of septic shock is the activation of host effecter cells by endotoxin and lipopolysaccharide (LPS) associated with cell membranes of gram-negative bacteria. For these reasons, the key point of treatment is removing LPS. S-thanatin (Ts), an analog of thanatin, was synthesized by substituting the 15th amino acid of threonine with serine, which showed a broad antimicrobial activity against gram-negative and gram-positive bacteria. We have reported its LPS-binding and -neutralizing activity in vitro. The aim of this study is to examine the LPS-neutralizing activities and the protective effects of S-thanatin in vivo. Every mice was injected intraperitoneally with LPS (from Escherichia coli O111:B4) 150 μg before injected intraperitoneally or vena caudalis with 3 mg/kg, 6 mg/kg and 12 mg/kg, and measured endotoxin and tumor necrosis factor alpha (TNF-α) concentrations in plasma, as well as lethality. The results showed that S-thanatin can significantly reduce endotoxin and TNF-α level in plasma, at the same time resulting in the highest survival rates.

Research highlights▶ Different treatment methods of S-thanatin experimental conditions were designed. ▶ Tumor necrosis factor alpha (TNF-α) and endotoxin concentrations in plasma were measured. ▶ S-thanatin can reduce endotoxin and TNF-α level in plasma and result in a highest survival rates. ▶ Different dosages of S-thanatin administration in mice showed different inhibitory effects.