Open AccessExperimental study of a novel phospholipase A 2 inhibitor in acute pancreatitis
Author(s) -
Uhl W.,
Schrag H.J.,
Schmitt ER N.,
Aufenanger J.,
Nevalainen T. J.,
Büchler M. W.
Publication year - 1998
Publication title -
british journal of surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.202
H-Index - 201
eISSN - 1365-2168
pISSN - 0007-1323
DOI - 10.1046/j.1365-2168.1998.00674.x
Subject(s) - acute pancreatitis , medicine , phospholipase a2 , pancreatitis , pancreas , pancreatic disease , gastroenterology , pharmacology , endocrinology , enzyme , biochemistry , biology
Background In acute pancreatitis, two different types of secretory phospholipase A 2 (PLA 2 ) have been found: pancreatic type I PLA 2 and non‐pancreatic type II PLA 2 . In this study a potent new PLA 2 inhibitor effective against type II PLA 2 was used in an experimental model of acute pancreatitis. Methods In 70 rats the efficacy of the compound was analysed in two experimental models of acute pancreatitis: cerulein‐ and taurocholate‐induced acute pancreatitis, imitating mild and severe disease respectively. Serum rat type I PLA 2 protein concentration and type I and type II PLA 2 catalytic activities were measured while giving the inhibitor therapeutically. In a prophylactic protocol the effect on histology was analysed. Results In the taurocholate model, type II PLA 2 activity was found to be nine‐fold higher than in the cerulein model ( P < 0·002), whereas the activity of type I PLA 2 was not increased. The inhibitor significantly decreased serum type II PLA 2 activity in the taurocholate model of acute pancreatitis ( P < 0·05) but type I PLA 2 protein concentration and type I PLA 2 activity were not affected. The inhibitor also reduced histological tissue damage, with significant differences at 3 and 12 h ( P < 0·01). Conclusion The PLA 2 inhibitor significantly reduced type II PLA 2 activity and was able to protect the pancreas against tissue damage. PLA 2 inhibition offers the possibility of a treatment for acute pancreatitis. © 1998 British Journal of Surgery Society Ltd