Beneficial effects of the synthetic trypsin inhibitor camostate in cerulein-induced acute pancreatitis in rats.
The therapeutic effect and the mechanism of action of the synthetic trypsin inhibitor camostate were studied in a rat model of acute interstitial pancreatitis induced by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats with acute pancreatitis were given either 100 mg/kg body weight camostate or volume- and pH-adjusted water via an orogastric tube 30 min after the last cerulein injection. The elevation of serum amylase activity was significantly reduced by camostate treatment and the peak value was seen 1 hr earlier than that observed in the rats that did not receive camostate. Camostate also inhibited the reduction in pancreatic content of lipase and amylase seen during experimental pancreatitis. These effects were accompanied by alleviation of the histologic signs of acute pancreatitis such as cellular infiltration and acinar cell vacuolization. After oral administration, camostate and its metabolite were absorbed from the intestine and were detectable in plasma for more than 6 hr in concentrations high enough to have antiprotease activity. In addition, camostate in the duodenum was able to increase pancreatic juice flow and protein output and to stimulate endogenous secretin release. These results suggest that oral administration of camostate reduces the severity of cerulein-induced acute pancreatitis by releasing endogenous secretin and by its antiprotease activity.
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
M
M
Otsuki
S
S
Tani
Y
Y
Okabayashi
M
M
Fuji
T
T
Nakamura
T
T
Fujisawa
H
H
Itoh
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002108:Ceruletide; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D011377:Proglumide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012633:Secretin / Q000097:blood; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D004952:Esters; D006146:Guanidines; D014361:Trypsin Inhibitors; C034532:camostat; D012633:Secretin; D016670:Gabexate; C045130:4-(4-guanidinobenzoyloxy)phenylacetic acid; D002108:Ceruletide; D000681:Amylases; D011377:Proglumide