Effect of protease inhibitor FUT-175 on acute hemorrhagic pancreatitis in mice.
The effect of FUT-175, a new synthetic trypsin inhibitor, was evaluated in a lethal model of acute hemorrhagic pancreatitis induced by feeding mice a choline-deficient, ethionine-supplemented diet (CDE diet). When FUT-175 was given prophylactically at doses of 20 mg/kg body wt, the survival rate was significantly improved (p less than 0.05). The serum amylase concentration and trypsin activity in serum were also significantly diminished (p less than 0.05). Prophylactic administration of 5 mg/kg body wt of FUT-175 showed a statistically significant decrease in the serum trypsin activity, but it did not improve the survival rate. Therapeutic administration of FUT-175 showed no favorable effect. FUT-175 showed protective effects on the course of severe acute pancreatitis only when given prophylactically at the beginning of the pancreatitis induced by the CDE diet.
Suzuki
M
M
Department of Surgery, University of California, Davis Medical Center, Sacramento 95817.
Isaji
S
S
Stanten
R
R
Frey
C F
CF
Ruebner
B
B
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001550:Benzamidines; D002794:Choline / Q000008:administration & dosage; D002796:Choline Deficiency / Q000150:complications; D004032:Diet / Q000009:adverse effects; D005001:Ethionine / Q000008:administration & dosage; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006146:Guanidines / Q000494:pharmacology*; D051379:Mice; D010195:Pancreatitis / Q000209:etiology / Q000517:prevention & control*; D014357:Trypsin / Q000097:blood; D014361:Trypsin Inhibitors / Q000494:pharmacology
D001550:Benzamidines; D006146:Guanidines; D014361:Trypsin Inhibitors; D000681:Amylases; D014357:Trypsin; D002794:Choline; D005001:Ethionine; C032855:nafamostat