Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: involvement of cyclooxygenases and heat shock protein 70

Abstract

Aim: 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.

Conclusion: 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.

Figure 1

Effect of sham operation (SO), IP, resveratrol (RES) or rofecoxib (ROF) applied alone or in combination on serum lipase activity (A), IL-1® (B), poly-C ribonuclease (C), pancreatic DNA synthesis (D), and pancreatic blood flow (E) in rats with or without cerulein-induced pancreatitis. ^aP<0.05 vs shamoperated rats treated with cerulein alone, ^bP<0.001 vs sham-operated salinetreated control (SO), ^cP<0.05 vs rats exposed to IP and treated with cerulein.

Figure 2

Representative Western blot analysis of b-actin protein (A) and HSP 70 (B), and the ratio of HSP 70 over b-actin protein (C) in pancreatic tissue of sham-operated control rats (lane 1), rats exposed to IP (lane 2), sham-operated rats with cerulein-induced pancreatitis (CIP, lane 3), and rats with IP applied prior to cerulein-induced pancreatitis (IP+CIP, lane 4). ^bP<0.001 vs sham-operated rats treated with cerulein alone (CIP), ^aP<0.05 vs sham-operated saline-treated control, ^dP<0.001 vs rats exposed to IP without induction of acute pancreatitis (CIP).