Experimental study of a novel phospholipase A2 inhibitor in acute pancreatitis

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.