Different effects of dexamethasone and the nitric oxide synthase inhibitor L-NAME on caerulein-induced rat acute pancreatitis, depending on the severity.
Effects of dexamethasone and N(G)-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on caerulein-induced acute pancreatitis were examined in rats. Acute pancreatitis was induced by caerulein (20 mug/kg, s.c.) given repeatedly 2 or 4 times every hour, and serum amylase levels, pancreas weight and myeloperoxidase (MPO) activity were measured 6 h after the first injection of caerulein. Dexamethasone (3 mg/kg) and L-NAME (30 mg/kg) were administered p.o. 30 min before the first injection of caerulein. Caerulein caused moderate or severe pancreatitis, depending on the times of injections, resulting in different degrees of increase in serum amylase levels and pancreas weight, and the marked elevation of MPO activity was observed only after injections of caerulein given 4 times per hour. Both dexamethasone and L-NAME suppressed the severity of pancreatits, yet the effect of L-NAME as compared with dexamethasone was more potent against mild pancreatitis but less potent against severe pancreatitis. These results suggest that caerulein-induced acute pancreatitis shows different responsiveness to L-NAME and dexamethasone, depending on the severity; the former is more effective against pancreatitis with less inflammation, while the latter is more effective against pancreatitis with severe inflammation. It is assumed that endogenous NO may be involved in oedema formation as the early event in the development of acute pancreatitis.
Sugiyama
Yusuke
Y
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kamigyo, Kyoto, 802-8566, Japan. sgym-ysk@koto.kpu-m.ac.jp
Kato
Shinichi
S
Abe
Mitsumasa
M
Mitsufuji
Shoji
S
Takeuchi
Koji
K
D000208:Acute Disease; D000284:Administration, Oral; D000681:Amylases / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002108:Ceruletide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; C032637:ceruletide diethylamine; D003907:Dexamethasone; D002108:Ceruletide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D000681:Amylases; D019331:NG-Nitroarginine Methyl Ester