EXPERIMENTAL-STUDY OF A NOVEL PHOSPHOLIPASE A(2) INHIBITOR IN ACUTE-PANCREATITIS

Background In acute pancreatitis, two different types of secretory pho spholipase 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) inhi bitor effective against type II PLA(2) was used in an experimental mod el of acute pancreatitis. Methods In 70 rats the efficacy of the compo und was analysed in two experimental models of acute pancreatitis: cer ulein-and taurocholate induced acute pancreatitis, imitating mild and severe disease respectively. Serum rat type I PLA(2) protein concentra tion 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 mod el, type II PLA(2) activity was found to be nine-fold higher than in t he cerulein model (P < 0.002), whereas the activity of type I PLA(2) w as 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) activit y were not affected. The inhibitor also reduced histological tissue da mage, with significant differences at 3 and 12 h (P < 0.01). Conclusio n The PLA(2) inhibitor significantly reduced type II PLA(2) activity a nd was able to protect the pancreas against tissue damage. PLA(2) inhi bition offers the possibility of a treatment for acute pancreatitis.