[Role of free radicals in the development of acute mild and severe pancreatitis in mice].
In order to clarify the role of free radicals in the pathogenesis of acute pancreatitis, we observed the effect of a new synthetic free radical scavenger (CV-3611) on the pathological state in the models of both caerulein and CDE-diet induced acute pancreatitis in mice. In both models of acute pancreatitis, the levels of serum amylase activity were reduced significantly by the treatment of CV-3611. Pancreatic edema formation was also reduced significantly at 3.5 and 9 h after the first caerulein i.p. injection. The 4 days survival rate in CDE-diet induced pancreatitis was significantly elevated from 41.2% to 81.3% by the treatment of CV-3611. These results indicate that this synthetic scavenger, which has a long circulation half life, high affinity to biomembrane and good cell penetration ability, is effective on the development of both severe and mild pancreatitis. The main pathogenesis of both models is suggested to be radical reactions on the biomembrane which is caused by the interreaction between endothelium and neurophile in caerulein induced pancreatitis, and by the lipid peroxidation on the biomembrane of the organella in the cell in CDE-diet induced pancreatitis.
Nonaka
A
A
First Department of Surgery, Faculty of Medicine, Kyoto University.
Manabe
T
T
Kyogoku
T
T
Tamura
K
K
Tobe
T
T
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002108:Ceruletide; D004727:Endothelium; D005001:Ethionine; D005260:Female; D005609:Free Radicals; D015227:Lipid Peroxidation; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy*
D005609:Free Radicals; D002108:Ceruletide; C061185:2-O-octadecylascorbic acid; D000681:Amylases; D001205:Ascorbic Acid; D005001:Ethionine