The protective effect of the trypsin inhibitor urinastatin on cerulein-induced acute pancreatitis in rats.

We examined the protective effects of the trypsin inhibitor, urinastatin, extracted from human urine in experimental acute pancreatitis in conscious rats. Acute pancreatitis was induced by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Urinastatin at a dose of 50,000 U/kg body weight/6.5 h was given by continuous i.v. infusion beginning 0.5 h before the first cerulein injection and continuing until 3 h after the last one, for a total of 6.5 h. Urinastatin significantly reduced serum levels of amylase, lipase, and anionic trypsin(ogen) but did not affect pancreatic wet weight or protein or enzyme content. Urinastatin also significantly reduced the degree of acinar cell vacuolization, interstitial edema, and cellular infiltration. These results suggest that urinastatin does not block the induction of acute pancreatitis by cerulein but does substantially reduce its severity.