2-o-octadecylascorbic-acid and Acute-Disease

To define the role of free radicals and of lipid peroxide involvement during the progress of cerulein-induced acute pancreatitis in mice, we evaluated the effect of a novel free radical scavenger, 2-octadecylascorbic acid (CV-3611), on pancreatic edema formation, and the levels of serum enzymes (amylase, lipase) and of lipid peroxide in pancreatic tissue. Mice were divided into three groups: control group, intraperitoneal injection of saline only; pancreatitis group, cerulein 50 micrograms/kg injected intraperitoneally six times at 1-hr intervals; treatment groups, CV-3611 10 mg/kg subcutaneously just after intraperitoneal cerulein injection. After the cerulein injection, the degree of pancreatic edema formation, serum amylase and lipase levels, and the amount of lipid peroxide in pancreatic tissue increased significantly during the observation period of 12 hr. Treatment with CV-3611 resulted in significant reduction in pancreatic edema formation at 3.5 hr (P less than 0.05) and 9 hr (P less than 0.05), serum amylase and lipase levels at 3.5 hr (P less than 0.05) and 12 hr (P less than 0.05), and lipid peroxide levels at 3.5 hr (P less than 0.05), 6 hr (P less than 0.05) and 12 hr (P less than 0.05). These results indicate that a novel free radical scavenger, CV-3611, has a strong therapeutic effect during the development of acute pancreatitis and suggest that oxygen-derived free radicals play an important role in the pathogenesis of acute pancreatitis.

Topics: Acute Disease; Amylases; Animals; Ascorbic Acid; Ceruletide; Female; Free Radical Scavengers; Lipase; Mice; Mice, Inbred BALB C; Pancreatitis; Peroxidases

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.

Topics: Acute Disease; Amylases; Animals; Ascorbic Acid; Ceruletide; Endothelium; Ethionine; Female; Free Radicals; Lipid Peroxidation; Mice; Mice, Inbred BALB C; Neutrophils; Pancreatitis