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.