Camostat, an oral trypsin inhibitor, reduces pancreatic fibrosis induced by repeated administration of a superoxide dismutase inhibitor in rats

J Gastroenterol Hepatol. 2005 Jun;20(6):895-9. doi: 10.1111/j.1440-1746.2005.03826.x.

Abstract

Background and aim: An oral trypsin inhibitor, camostat (CM), has a beneficial effect on chronic pancreatitis, but its mechanism is not yet fully understood. Recently, pancreatic stellate cells (PSC) have been reported to play an essential role in pancreatic fibrosis. An experimental model of pancreatic fibrosis induced by a superoxide dismutase (SOD) inhibitor (diethyldithiocarbamate [DDC]) was developed in rats. Thus, the effect of an oral trypsin inhibitor on pancreatic fibrosis and PSC was investigated.

Methods: Pancreatic fibrosis was induced in rats using DDC (DDC rats). DDC + CM rats were administered DDC, and subsequently were fed a diet containing CM. Immunohistochemistry of the pancreas was performed with monoclonal anti-alpha-smooth muscle actin (alpha-SMA) antibody and anti-desmin antibody.

Results: The DDC rats showed a significant increase in alpha-SMA-positive cells or desmin-positive cells compared with control rats. These significant increases in the fibrotic area improved after treatment with CM. The level of prolyl hydroxylase in the pancreas, which significantly increased as a result of DDC, decreased after treatment with CM.

Conclusion: Camostat has a beneficial effect on pancreatic fibrosis induced by the administration of a SOD inhibitor, which inhibits the proliferation and activation of PSC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Disease Models, Animal
  • Ditiocarb / administration & dosage
  • Ditiocarb / toxicity
  • Drug Administration Schedule
  • Fibrosis / drug therapy
  • Fibrosis / pathology
  • Gabexate / administration & dosage
  • Gabexate / analogs & derivatives*
  • Gabexate / therapeutic use
  • Male
  • Pancreas / drug effects
  • Pancreas / enzymology
  • Pancreas / pathology*
  • Pancreatic Diseases / chemically induced
  • Pancreatic Diseases / drug therapy*
  • Pancreatic Diseases / pathology
  • Procollagen-Proline Dioxygenase / metabolism
  • Rats
  • Rats, Wistar
  • Severity of Illness Index
  • Treatment Outcome
  • Trypsin Inhibitors / administration & dosage*
  • Trypsin Inhibitors / therapeutic use

Substances

  • Trypsin Inhibitors
  • camostat
  • Gabexate
  • Ditiocarb
  • Procollagen-Proline Dioxygenase