Effective peritoneal therapy of acute pancreatitis in the rat with glutaryl-trialanin-ethylamide: a novel inhibitor of pancreatic elastase.
The six hour peritoneal lavage with glutaryl-trialanin-ethylamide, a low molecular competitive inhibitor of pancreatic elastase (IC50-8 mumol/l), effectively suppresses the evolution of taurocholate induced acute pancreatitis in the rat. The lavage alone is followed by a marked decrease of fat necrosis and amylase and lipase activity in serum. The area of pancreatic haemorrhage was significantly reduced only after the lavage solution was supplemented with Glt-Ala3-NHEt. The effect was not enhanced by a bolus injection of the inhibitor before starting the lavage. The combination of Glt-Ala3-NHEt with aprotinin or nafamstate mesilate produced only marginal greater benefit. The effect of Glt-Ala3-NHEt on pancreatic haemorrhage is time and dose related even with delayed onset of the lavage. Animals treated with peritoneal lavage without Get-Ala3-NHEt lived longer than controls (p less than 0.05), but by 60 hours the survival rate of both groups was almost the same (76 v 74%). All animals lavaged with Glt-Ala3-NHEt survived 120 hours and the difference in the survival rate between this and both remaining groups was significant (100% v 76% v 74% - p less than 0.05). The results were considered favourable and preliminary clinical trials of Glt-Ala3-NHEt in subjects with acute pancreatitis justified.
Fric
P
P
Department of Medicine, Charles University, Prague, Czechoslovakia.
Slabý
J
J
Kasafírek
E
E
Kocna
P
P
Marek
J
J
D000681:Amylases / Q000097:blood; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005218:Fat Necrosis / Q000517:prevention & control; D008049:Lipase / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D010533:Peritoneal Lavage; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid; D013997:Time Factors
D009842:Oligopeptides; D013656:Taurocholic Acid; C044877:glutaryl-alanyl-alanyl-alanyl-ethylamide; D008049:Lipase; D000681:Amylases; D010196:Pancreatic Elastase