Therapeutic effect of basic fibroblast growth factor on experimental pancreatitis in rat.
Basic fibroblast growth factor (bFGF) is one of the mitogens that facilitate endothelial proliferation and angiogenesis. This study was designed to examine the therapeutic effect of bFGF on experimental pancreatitis in rat. Edematous pancreatitis was induced by intraperitoneal injections of cerulein (50 microg/kg) at hourly intervals. BFGF (70 nmol/kg) was administered intraperitoneally after induction of pancreatitis. DNA synthesis of isolated pancreatic acinar cells of normal rats was determined as the uptake of 5-bromo-2'-deoxyuridine (BrdU) into the cells. Immunohistochemical staining of DNA synthesis in acinar cells during cerulein-induced pancreatitis was also examined with BrdU labeling in vivo technique. Cerulein administration increased serum amylase, lipase level, and wet weight of pancreatic tissue. Treatment with bFGF markedly ameliorated all these parameters. In primary culture system of isolated pancreatic acinar cells of normal rats, bFGF caused a dose-dependent increase in BrdU incorporation into DNA, showing an EC50 value of 0.8 nmol/L and a maximum response of 2.5-fold increase at a concentration of 400 nmol/L. bFGF treatment (70 nmol/kg) markedly increased BrdU labeling in the nucleus of acinar cells of the pancreatitis rats group in immunohistochemical examination when compared with control without bFGF treatment. Treatment with bFGF may represent a promising therapeutic concept for patients with acute pancreatitis.
Hosokawa
M
M
Department of Metabolism and Clinical Nutrition, Faculty of Medicine, Kyoto University, Japan. hosokawa@metab.kuhp.kyoto-u.ac.jp
Tsukada
H
H
Fukuda
F
F
Oya
M
M
Onomura
M
M
Nakamura
H
H
Kodama
M
M
Fujita
J
J
Seino
Y
Y
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D002108:Ceruletide / Q000008:administration & dosage; D004247:DNA / Q000096:biosynthesis; D004487:Edema / Q000188:drug therapy; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D016222:Fibroblast Growth Factor 2; D002108:Ceruletide; D004247:DNA; D001973:Bromodeoxyuridine