The present study investigates the effect of oral pretreatment with the
protease inhibitor camostate on the outcome of
pancreatitis in three experimental models. In
pancreatitis induced by overstimulation with
cholecystokinin (CCK) in rats, pancreatic
enzymes and the histological degree of
pancreatitis were quantified; in
pancreatitis induced by a
choline-deficient
ethionine-supplemented (CDE) diet in mice, the effect on survival was monitored; and in bile-induced
pancreatitis in rats, the effect on survival, pancreatic
enzymes, and histology was studied. Feeding of
camostate (200 mg/kg/day) for 2 weeks worsened the histological degree of
pancreatitis induced by overstimulation with CCK or by injection of
taurocholate. The concentration of
amylase in the pancreas and in serum was significantly lower after pretreatment with
camostate, both in
cerulein-induced
pancreatitis and in bile-induced
pancreatitis, while the concentration of
trypsin in the pancreas was significantly increased in the
camostate-treated animals. Pretreatment with
camostate significantly lowered survival. In
pancreatitis induced by a CDE diet, 3 of 20 mice survived the observation period, while 9 of 20 control animals survived (p < 0.05). In
taurocholate-induced
pancreatitis, 5 of 29 rats were alive after 3 days versus 18 of 30 animals in the control group (p < 0.001). CCK levels were not elevated in
camostate-treated rats, when
pancreatitis was induced 24 h after finishing
camostate feeding. It is concluded that
camostate induced pancreatic
hypertrophy and increased concentration of
proteolytic enzymes aggravate experimental panceatitis and that this is not mediated by increased CCK levels.