PANCREATIC PROTEASES INHIBITION IS NOT EFFECTIVE IN AMELIORATING PERITONITISINDUCED CELL ACTIVATION, ORGAN DAMAGE, AND MORTALITY IN RATS

Abstract

Background: Intestinal pancreatic proteases have been supposed to be involved in aggravating intestinal damage, by proteolytic cleavage, resulting in leukocyte activation, organ damage, and death. Aim: We determined, if pancreatic proteases inhibition (PPI) ameliorates peritonitis-induced inflammatory response, organ damage and death in rats. Methods: Anaesthetized rats underwent midline laparotomy. Caecum contents were collected by puncturing, diluted with saline 1:2, and placed into the four quadrants of the abdominal cave (0.5 mL each). After 3 hours, all animals received standard antibiotic regimen, underwent a re-laparotomy followed by intraperitoneal lavage (20 mL saline/quadrant), and intestinal lavage with Ringer's solution (4 mL/min for 25 min) with or without protease inhibitor gabexate mesilate (0.37 mM). Blood samples were collected at baseline, 5 and 24 hours after the onset of peritonitis. The 7-day survival rate was followed. CD11b and oxidative burst was determined by flow cytometry. Results: Peritonitis-induced increase in CD11b was not affected by PPI [266 (21/ 44) vs. 296 (25/44) % changes vs. baseline]. Similarly, PPI did not affect the oxidative burst [158 (14/72) vs. 110 (12/41), % changes vs. baseline at 5 hrs. PPI did neither affect the peritonitis- induced organ damage reflected in an increase in transaminases and creatinine nor the 7-day survival rate in rats. Conclusion: Our data suggest that intestinal pancreatic proteases are not involved in peritonitis associated inflammatory response, organ failure, and death in rats.