Effect of a new inhibitor of type II phospholipase A2 on experimental acute pancreatitis in rats.
The catalytic activity of type II phospholipase A2 (PLA2) in blood has been reported to increase in acute pancreatitis and to reflect the severity of pancreatitis. In this study, we evaluated the effects of a new inhibitor of type II PLA2, S5920/LY315920Na, on trypsin-taurocholate-induced pancreatitis in rats. Hemorrhagic pancreatitis was induced by an infusion of a mixture of trypsin and taurocholate into the pancreatic duct. S5920/LY315920Na was administered subcutaneously at 0 h and 3 h after the induction of pancreatitis. Survival rates for 24 h in rats treated with 0.1 and 1 mg/kg of S5920/LY315920Na were significantly higher than that in untreated rats (71 and 86% vs. 14%). Serum levels of amylase and lipase in rats treated with 1 mg/kg of S5920/LY315920Na were significantly lower than those in untreated rats (amylase, 6,903 vs. 32,516 U/L; and lipase, 514 vs. 6,710 U/L) at the time of death or 24 h after the induction of pancreatitis. Plasma levels of S5920/LY315920Na were enough to inhibit catalytic activity of PLA2 in plasma for 9 h. A new inhibitor of type II PLA2, S5920/LY315920Na, inhibited catalytic activity of PLA2 and improved the survival rate in experimental hemorrhagic pancreatitis in rats.
Yoshikawa
T
T
Department of Internal Medicine II, Nagoya University School of Medicine, Japan.
Naruse
S
S
Kitagawa
M
M
Ishiguro
H
H
Nakae
Y
Y
Ono
T
T
Hayakawa
T
T
D000085:Acetates / Q000494:pharmacology*; D000208:Acute Disease; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006470:Hemorrhage; D007211:Indoles / Q000494:pharmacology*; D007651:Keto Acids; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000097:blood; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D013656:Taurocholic Acid / Q000633:toxicity; D014357:Trypsin / Q000633:toxicity
D000085:Acetates; D004791:Enzyme Inhibitors; D007211:Indoles; D007651:Keto Acids; C117948:varespladib; D013656:Taurocholic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D014357:Trypsin