Abstract
Background and Objective: Inflammatory cytokines and leukocytes recruitment to the injury site are involved in the pathogenesis of acute pancreatitis. This study aimed to determine whether metformin can ameliorate TNF-alpha-CD45 axis mediated acute pancreatitis associated with the augmentation of p-AMPKand inhibition of biomarkers of acute pancreatic injury. Materials and Methods: The model group of rats received 2 injections of L-argi nine (2.5 g kg(-1)) at 1 hr intervals before being sacrificed after 48 hrs, whereas, the protection group started metformin (50 mg kg(-1)) treatment daily for 2 weeks before L-arginine injections and continued on metformin until the end of the experiment. Results: L-arginine significantly (p<0.0001) induced inflammation (TNF-alpha mRNA) and leukocyte recruitment as demonstrated by an increased leukocyte common antigen (CD45) immunostaining, which was substantially protected by metformin. Metformin also significantly inhibited L-arginine-modulated blood and tissue levels of amylase, LDH, IL-10 mRNA, phosphorylated AMPK. In addition, a significant correlation between the TNF-alpha-CD45 axis and biomarkers of acute pancreatitis as well as AMPK, was observed. Conclusion: These findings show substantial protection by metformin against L-arginine-induced TNF-alpha-CD45 axis mediated acute pancreatitis associated with the upregulation of pancreatic AMPK and down regulation of acute pancreatic injury biomarkers.