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


CONCLUSIONS
Camostat has a beneficial effect on pancreatic fibrosis induced by the administration of a SOD inhibitor, which inhibits the proliferation and activation of PSC.
Emori
Yasuyuki
Y
Department of Laboratory Medicine, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Mizushima
Takaaki
T
Matsumura
Naoki
N
Ochi
Koji
K
Tanioka
Hiroaki
H
Shirahige
Akinori
A
Ichimura
Mitsuko
M
Shinji
Toshiyuki
T
Koide
Norio
N
Tanimoto
Mitsune
M
D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004050:Ditiocarb / Q000008:administration & dosage / Q000633:toxicity; D004334:Drug Administration Schedule; D004952:Esters; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology; D016670:Gabexate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006146:Guanidines; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D010182:Pancreatic Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014361:Trypsin Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use
D004952:Esters; D006146:Guanidines; D014361:Trypsin Inhibitors; C034532:camostat; D016670:Gabexate; D004050:Ditiocarb; D011393:Procollagen-Proline Dioxygenase