Dysregulation of the glycoprotein zymogen granules in pancreatic acinar cells in acute pancreatitis: differential protection by vitamin E and metformin

We investigated whether induction of acute pancreatitis (AP) can cause dysregulation in the glycoprotein zymogens, following episodes of nitrosative stress, which may be differentially protected by vitamin E and metformin. AP was induced in rats by L-arginine (2.5 g/kg) injections (two doses given at 1-h interval). The protective groups were pre-treated with either vitamin E (60 mg/kg) or metformin (50 mg/kg) prior to L-arginine injections and continued on these medications until being sacrificed. AP markedly decreased the density of zymogen granules in pancreatic acinar cells (44.5 +/- 2.2% in control versus 9.2 +/- 1.9% in AP), alongside tissue damage and a significant (p < 0.0001) increase in biomarkers of nitrosative stress (iNOS), inflammation (IL-6 and TNF-alpha mRNA), and pancreatic injury (amylase, lipase, LDH, and MPO). All these parameters were significantly (p <= 0.0005) protected by vitamin E and metformin, with vitamin E providing greater protection for pancreatic glycoprotein zymogens and serum amylase. Thus, AP is associated with the destruction of the glycoprotein zymogens, which is differentially protected by vitamin E and metformin.