Effect of camostate administration for two weeks on experimental pancreatitis in mice and rats.
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.
Leonhardt
U
U
Zentrum Innere Medizin, Abteilung Gastroenterologie und Endokrinologie, Göttingen, Germany.
Seidensticker
F
F
Stöckmann
F
F
Creutzfeldt
W
W
D000284:Administration, Oral; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000097:blood; D004952:Esters; D005260:Female; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051379:Mice; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D004952:Esters; D006146:Guanidines; D011480:Protease Inhibitors; C034532:camostat; D016670:Gabexate; D002766:Cholecystokinin; D000681:Amylases