Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: involvement of cyclooxygenases and heat shock protein 70.
OBJECTIVE
To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process.


METHODS
In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg).


RESULTS
IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-1beta. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis.


CONCLUSIONS
Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70.
Warzecha
Zygmunt
Z
Department of Physiology, Jagiellonian University Medical College, ul. Grzegorzecka 16, Kraków 31-531, Poland.
Dembinski
Artur
A
Ceranowicz
Piotr
P
Konturek
Stanislaw-J
SJ
Dembinski
Marcin
M
Pawlik
Wieslaw-W
WW
Tomaszewska
Romana
R
Stachura
Jerzy
J
Kusnierz-Cabala
Beata
B
Naskalski
Jerzy-W
JW
Konturek
Peter-C
PC
D000818:Animals; D002108:Ceruletide / Q000633:toxicity; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004487:Edema / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D019194:Ischemic Preconditioning; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D018840:HSP70 Heat-Shock Proteins; D007375:Interleukin-1; D007783:Lactones; D013267:Stilbenes; D013450:Sulfones; C116926:rofecoxib; D016753:Interleukin-10; D002108:Ceruletide; D011451:Prostaglandin-Endoperoxide Synthases; D000077185:Resveratrol