Protective effects of gabexate mesilate on acute pancreatitis induced by tacrolimus (FK-506) in rats in which the pancreas was stimulated by caerulein

Tetsuhide Ito, Toshinari Kimura, Masayuki Furukawa, Hiroya Yamaguchi, Masayoshi Goto, Itsuro Nakano, Hajime Nawapa

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Abstract

We investigated the acute effects of the immunosuppressive agent, tacrolimus (FK-506), on the exocrine pancreas, in rats with or without stimulation of the pancreas, in rats with or without stimulation of the pancreas, and evaluated the protective effects exerted by gabexate mesilate (FOY). While an intravenous injection of FK-506 did not change serum amylase levels during the 5-h observation period, this agent increased pancreatic amylase and protein content, and decreased the content of pancreatic DNA. Histologically, we observed intra-acinar vacuolization and individual cell necrosis. When the pancreas was stimulated by two intraperitoneal injections of caerulein (5 μg/kg) at 1-h intervals, however, which treatment did not induce any evident pancreatic change, FK-506 significantly increased serum amylase, pancreatic wet weight, and pancreatic amylase and protein, and decreased pancreatic DNA. Histologically, there were significant dose-related differences in the severity of intra-acinar vacuolization, interstitial edema, neutrophil infiltration, individual cell necrosis, and hemorrhage. Levels of intrapancreatic elastase were elevated and local pancreatic blood flow was reduced. Treatment with FOY improved the FK-506-induced acute pancreatitis, but did not increase the pancreatic blood flow. These findings indicate that FK-506 enhances abnormal pancreatic enzyme secretion and suggest that therapeutic doses of this agent can induce acute pancreatitis when the pancreas is stimulated. A protease inhibitor may protect the exocrine pancreas in patients who receive FK-506 after organ transplantation.

Original languageEnglish
Pages (from-to)305-313
Number of pages9
JournalJournal of gastroenterology
Volume29
Issue number3
DOIs
Publication statusPublished - Jun 1 1994

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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