Nonsteroidal anti-inflammatory drugs alleviate severity of post-endoscopic retrograde cholangiopancreatography pancreatitis by inhibiting inflammation and reducing apoptosis.

Abstract

The prophylactic effect of nonselective nonsteroidal anti-inflammatory drugs on post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis has been observed for a long time. However, whether the selective nonsteroidal anti-inflammatory drugs possess similar abilities and the mechanisms by which nonsteroidal anti-inflammatory drugs work remain unclear. The present study aimed to determine the protective effects of nonsteroidal anti-inflammatory drugs on post-ERCP pancreatitis in a rat model and examine underlying mechanisms. Thirty-two female rats were equally and randomly divided into four groups: the sham group, post-ERCP pancreatitis model group, indomethacin-pretreated group, and parecoxib-pretreated group. Indomethacin or parecoxib was delivered 30min prior to surgery; 24h after post-ERCP pancreatitis establishment, the rats were sacrificed. Serum amylase and lipase activities, inflammatory cytokine release, pancreatic histopathological scores, neutrophil infiltration, and the expression pattern cyclooxygenase at the protein level and pancreatic apoptosis were quantified and analyzed. Both indomethacin and parecoxib inhibited the activities of serum amylase and lipase and reduced the severity of pancreatic histopathology. Mechanistically, both drugs decreased the expression level of cyclooxygenase 2; however, they had no influence on the cyclooxygenase 1 protein level. Moreover, they reduced inflammatory cytokine release, neutrophil infiltration into the pancreas, and NF-κB p65 activation. Notably, we found that apoptotic cells in the pancreas were remarkably diminished after the administration of both nonsteroidal anti-inflammatory drugs. Both selective and nonselective nonsteroidal anti-inflammatory drugs exert protective effects against post-ERCP pancreatitis by restraining inflammation and reducing acinar cell apoptosis through the inhibition of cyclooxygenase 2.