The use of antiendotoxin peptides in obstructive jaundice endotoxemia

Abstract

Two novel antiendotoxin peptides, P6 and C1, may reduce the inflammatory response. This study aimed to determine the effect of endotoxin on hepatic cytokine response and to assess P6 and C1-related attenuation of the proinflammatory response to endotoxemia, in experimental biliary obstruction. 15 Male Wistar rats were randomized to one of three groups: bile duct ligation (BDL)+P6 (n=5), BDL+C1 (n=5), and BDL+no peptide (n=5). Rats were weighed and underwent BDL surgery on day 1. On day 8, the rats were reweighed and isolated hepatic perfusion was carried out. P6 or C1 peptide (10 μmol/l) was preincubated with 300 ml of endotoxin-containing Krebs perfusate. After perfusion of 10 min with endotoxin-free perfusate, the livers were perfused for another 10 min with 300 ml of perfusate-containing endotoxin on its own or endotoxin plus peptide. This was followed by a further 100 min of perfusion with endotoxin-free perfusate. Effluent perfusate was collected at 20-min intervals for subsequent biochemical and cytokine analyses. Perfusion with endotoxin+P6 or endotoxin+C1 resulted in no significant difference in weight loss, or interleukin-6 response compared with perfusion with endotoxin alone. However, perfusion with endotoxin+P6 or endotoxin+C1 significantly reduced the tumor necrosis factor-α response to portal endotoxemia compared with perfusion with endotoxin alone. This study demonstrates that novel antiendotoxin peptides may attenuate the hepatic inflammatory response in portal endotoxemia. In obstructive jaundice, preoperative peptide administration may reduce endotoxin-related postoperative complications.