Human urinary trypsin inhibitor, urinastatin, prevents pancreatic injuries induced by pancreaticobiliary duct obstruction with cerulein stimulation and systemic hypotension in the rat.
OBJECTIVE
The protective effects of human urinary trypsin inhibitor against pancreatic injuries in multifactor-related experimental model of acute pancreatitis were evaluated.


METHODS
Experimental study.


METHODS
Acute pancreatitis was induced by short-termed (1-hour) pancreatico-biliary duct obstruction with cerulein stimulation (30 minutes; 0.2 microgram/kg per hour) and systemic hypotension (30 minutes; 30% reduction of mean arterial pressure) in rats. In this model, the protective effects of UTI against pancreatic injuries were evaluated at a dose of 10,000 U/kg per hour.


RESULTS
In this model, significant increases in portal serum amylase, cathepsin B and malate dehydrogenase levels were observed as compared with the control rats. The redistribution of cathepsin B from the lysosomal to the zymogen fraction and activation of trypsinogen were also observed. Moreover, the increased lysosomal and mitochondrial fragility as well as impaired pancreatic adenylate energy metabolism were noted. The therapeutic administration of human urinary trypsin inhibitor had significant protective effects against these pancreatic injuries. Furthermore, the combined prophylactic and therapeutic administration of human urinary trypsin inhibitor had more significant protective effects than only therapeutic treatment.


CONCLUSIONS
These results suggest the importance of timing and of selecting a pertinent protease inhibitor, such as urinary trypsin inhibitor, in the treatment of pancreatitis.
Hirano
T
T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Manabe
T
T
D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000032:analysis; D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000681:Amylases / Q000097:blood; D000818:Animals; D002401:Cathepsin B / Q000032:analysis; D002108:Ceruletide; D002779:Cholestasis / Q000150:complications*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006023:Glycoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D007022:Hypotension / Q000150:complications*; D007262:Infusions, Intravenous; D008291:Malate Dehydrogenase / Q000032:analysis; D008297:Male; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000032:analysis; D014361:Trypsin Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D006023:Glycoproteins; D014361:Trypsin Inhibitors; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D002108:Ceruletide; D000255:Adenosine Triphosphate; D008291:Malate Dehydrogenase; D000681:Amylases; D014357:Trypsin; D002401:Cathepsin B; C028665:urinastatin