Investigation of the effects of verapamil, dantrolene and 2-aminoethoxydiphenyl borate on caerulein induced acute pancreatitis in rats

Acute pancreatitis is an acute inflammatory disease of the pancreas, with variable involvement of other regional tissues or remote organ systems. Gallstones and alcohol are the commonest causes of acute pacreatitis. Altough etiologic factors of acute pacreatitis have been known, the pathophysiology has not been elucidated yet. The premature activation of digestive zymogens within acinar cells prior to reaching the duodenum has been proposed as a critical step in the pathogenesis of pancreatitis. Pathological intraacinar zymogen activation is associated with an aberrant rise in intracellular Ca+2.We hypothesized that calcium channel blocker such as 2-APB, Dantrolene and Verapamil for IP3R, RyR and L-type voltage-gated calcium channel respectively, could ameliorate cerulein-induced acute pacreatitis in rats. For that purpose, we measured amylase and lipase levels in serum and trypsin, trypsinogen, TAP, PSTI and Cathepsin B levels in pancreatic tissue. These biochemical measurements have been supported by histopathological observations. In our results, we found that increased amylase, lipase, trypsin and TAP levels in cerulein group, significantly decreased by calcium channel blockers. Additionally, while there is no important difference in Cathepsin B level, PSTI and Tripsinogen levels decreased among all groups.Consequently, our findings show that calcium channel blockers can have therapeutic effects on cerulein-induced AP. But it needs further advanced molecular analysis to elucidate pathophysiological mechanisms related with aberrant rise in intracellular [Ca+2] in acute pancreatitis.