Effect of urinary trypsin inhibitor on pancreatic cellular and lysosomal fragility in cerulein-induced acute pancreatitis in rats.
We evaluated the protective effect and the mechanism of action of the trypsin inhibitor, urinastatin, extracted from human urine, in experimental acute pancreatitis induced by a supramaximal dose of cerulein (5 micrograms/kg/hr for 3.5 hr). Urinastatin in a dose of 10,000 units/kg/hr was given by three different methods of continuous infusion: (1) 2 hr before and during cerulein infusion, (2) only during cerulein infusion, and (3) starting 1 hr after the beginning of cerulein infusion and continued for 3.5 hr. In protocol 1 and 2 urinastatin was significantly more protective than in 3. In protocol 1 urinastatin was very protective in all parameters tested (serum amylase level, pancreatic water and amylase content, distribution of lysosomal enzymes, cellular and lysosomal fragility). These results suggest that the administration of urinastatin before and during cerulein infusion may suppress the pathogenesis and evolution of pancreatitis by inhibiting the chain reaction of pancreatic enzyme activation closely related to redistribution of lysosomal enzyme and lysosomal fragility.
Hirano
T
T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Manabe
T
T
Tobe
T
T
D000208:Acute Disease; D000681:Amylases / Q000032:analysis / Q000187:drug effects; D000818:Animals; D002401:Cathepsin B / Q000032:analysis / Q000187:drug effects; D002108:Ceruletide; D004353:Drug Evaluation, Preclinical; D005110:Extracellular Space / Q000737:chemistry / Q000187:drug effects; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000187:drug effects; D008247:Lysosomes / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014361:Trypsin Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D006023:Glycoproteins; D014361:Trypsin Inhibitors; D002108:Ceruletide; D007770:L-Lactate Dehydrogenase; D000681:Amylases; D002401:Cathepsin B; C028665:urinastatin