INHIBITION OF SERUM PHOSPHOLIPASE-A(2) IN ACUTE-PANCREATITIS BY PHARMACOLOGICAL AGENTS IN-VITRO

Phospholipase-A(2) has been suggested as having a role in the pathophy siology of acute pancreatitis. The inhibition of phospholipase-A(2) wa s studied in vitro using 17 pharmacological agents in the search for a specific therapy for acute pancreatitis. The inhibitory effect was te sted using an isotopic assay system with 2-palmitoyl-(1-C-14)-labelled dipalmitoyl phosphatidylcholine as a substrate and 10 mu l of serum f rom patients with acute necrotizing pancreatitis as an enzyme source. Among all agents tested, anti-inflammatory drugs inhibited enzyme acti vity most significantly: indomethacin (9.0x10(-3) mol l(-1)) decreased the phospholipase-A(2) activity to one-tenth. The weak inhibitory eff ect could also be demonstrated using a lower concentration of 2x10(-5) mol l(-1), which can be achieved after intravenous administration of 50 mg of this drug. The other drugs inhibited the enzyme activity at c oncentrations higher than those achieved after intravenous injections in clinical use. Diclofenac (3.1x10(-2) mol l(-1)) reduced the phospho lipase-A(2) activity by 93%, ketoprofen (2.0x10(-2) mol l(-1)) or chlo rpromazine (1.4x10(-2) mol l(-1)) by 90%, tobramycin (1.7x10(-2) mol l (-1)) by 84%, doxycycline (9.0x10(-3) mol l(-1)) by 61%, dexamethasone (1.7x10(-3) mol l(-1)) by 62%, methylprednisolone (3.8x10(-2) mol l(- 1)) by 50%, and pindolol (1.0x10(-4) mol l(-1)) by 59%. A weak inhibit ion of phospholipase-A(2) activity was demonstrated by betamethasone, bupivacaine, digoxin, hydrocortisone, lidocaine, metoprolol, propranol ol, and vancomycin. Indomethacin proved the most potent of the tested agents in inhibiting phospholipase-A(2) activity in serum from patient s with acute pancreatitis and should be further studied in vivo.