Experimental study of a novel phospholipase A2 inhibitor in acute pancreatitis.

Abstract

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).

CONCLUSION:

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.

• Authors: W Uhl, H J Schrag, N Schmitter, J Aufenanger, T J Nevalainen, M W Büchler
• Journal: The British journal of surgery (Br J Surg) Vol. 85 Issue 5 Pg. 618-23 (May 1998) ISSN: 0007-1323 [Print] England
• PMID: 9635806 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Taurocholic Acid
• Ceruletide
• Phospholipases A
• Phospholipases A2

Topics

• Acute Disease
• Animals
• Ceruletide
• Edema
• Enzyme Inhibitors (therapeutic use)
• Female
• Necrosis
• Pancreatitis (chemically induced, drug therapy, enzymology, pathology)
• Phospholipases A (antagonists & inhibitors)
• Phospholipases A2
• Rats
• Rats, Wistar
• Taurocholic Acid