Experimental study of a novel phospholipase A2 inhibitor in acute pancreatitis.
BACKGROUND
In acute pancreatitis, two different types of secretory phospholipase A2 (PLA2) have been found: pancreatic type I PLA2 and non-pancreatic type II PLA2. In this study a potent new PLA2 inhibitor effective against type II PLA2 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 PLA2 protein concentration and type I and type II PLA2 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 PLA2 activity was found to be nine-fold higher than in the cerulein model (P < 0.002), whereas the activity of type I PLA2 was not increased. The inhibitor significantly decreased serum type II PLA2 activity in the taurocholate model of acute pancreatitis (P < 0.05) but type I PLA2 protein concentration and type I PLA2 activity were not affected. The inhibitor also reduced histological tissue damage, with significant differences at 3 and 12 h (P < 0.01).


CONCLUSIONS
The PLA2 inhibitor significantly reduced type II PLA2 activity and was able to protect the pancreas against tissue damage. PLA2 inhibition offers the possibility of a treatment for acute pancreatitis.
Uhl
W
W
Department of Visceral and Transplantation Surgery, University Hospital of Bern, Switzerland.
Schrag
H J
HJ
Schmitter
N
N
Aufenanger
J
J
Nevalainen
T J
TJ
Büchler
M W
MW
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D004487:Edema; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D009336:Necrosis; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid
D004791:Enzyme Inhibitors; D013656:Taurocholic Acid; D002108:Ceruletide; D010741:Phospholipases A; D054467:Phospholipases A2