The
therapeutic effects of
CV 3611, a new synthetic
free radical scavenger prepared from an
ascorbic acid derivative, on
choline deficient,
ethionine enriched (CDE) diet induced
acute pancreatitis in mice were evaluated and compared with those of
superoxide dismutase. Time/course studies after
subcutaneous injection of
CV 3611 in normal mice showed a peak plasma concentration of mean (SEM) 0.54 (0.09) micrograms/ml at one hour, with a gradual decrease over the next 10 hours, while a peak concentration in pancreatic tissue of mean (SEM) 425 (33) ng/g tissue was achieved at three hours and the
drug was undetectable at 12 hours. Survival rates and activities of pancreatic
enzymes (
amylase,
lipase,
elastase I) were compared in control mice and animals that received
CV 3611 before or at the time of feeding the CDE diet. The survival rate was observed in a no treatment group and mice given pretreatment or treatment with
CV 3611 or
superoxide dismutase. The survival rate was significantly better in the treatment group given
CV 3611 (p less than 0.02), but
superoxide dismutase had no significant effect on survival. The increases in the three serum
enzyme activities were significantly less at 48 hours in the groups given pretreatment or treatment with
CV 3611 than in the no treatment group. These results indicate that
CV 3611, which has been proved to pass through the cell membrane and to have a long half life in plasma and tissue, had an important therapeutic effect on the development of
acute pancreatitis. They also suggest that
oxygen derived
free radicals may play an important role in the development of
acute pancreatitis.