Epidermal growth factor protects against pancreatic damage in cerulein-induced pancreatitis.
Epidermal growth factor (EGF) exhibits gastroprotective and ulcer-healing action. These observations prompted us to determine the influence of EGF on cerulein-induced pancreatitis (CIP) in the rat. Acute pancreatitis was induced by subcutaneous infusion of cerulein (10 microg/kg/h) for 5 h. Initially EGF was administrated twice at doses of 1, 5, 10 or 100 microg/kg s.c. (first injection 30 min prior to cerulein infusion, and the second injection 2.5 h after the start of cerulein infusion) and from this part of study 10 microg/kg was chosen for the next experiments. CIP led to a significant decrease in DNA synthesis and a reduction in pancreatic blood flow (PBF) by 42 and 30%, respectively, as well as a significant increase in pancreatic weight, plasma amylase concentration, plasma interleukin-1beta (IL-1beta) level and the development of the histological signs of pancreatic damage with marked edema, leukocyte infiltration and vacuolization of acinar cells. Treatment with EGF attenuated the pancreatic tissue damage in CIP as manifested by partial reversal of the drop in DNA synthesis and improvement of pancreatic histology. Moreover, EGF administration attenuated the fall in PBF and significantly reduced the cerulein-evoked increase in pancreatic weight. Also plasma amylase and IL-1beta were decreased in rats treated with EGF. We conclude that: (1) EGF exerts a protective effect against CIP, and (2) the beneficial activity of EGF in CIP seems to depend on the increase in pancreatic cell proliferation, the reduction in cytokine generation and the attenuation of the fall in PBF.
Department of Physiology, College of Medicine, Jagiellonian University, Krakow, Poland.
Z
Z
Warzecha
A
A
Dembiński
P C
PC
Konturek
P
P
Ceranowicz
S J
SJ
Konturek
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D005765:Gastrointestinal Agents; D004815:Epidermal Growth Factor; D002108:Ceruletide; D004247:DNA