Targeting the Dysregulation of Pancreatic AMPK-iNOS-p53 Axis by Metformin in a Rat Model of L-arginine-Induced Acute Pancreatitis

A severe form of the inflammatory disease, acute pancreatitis, can induce multiple organ failure, leading to a high mortality rate. Little is known about the negative interaction between AMP-activated protein kinase (AMPK) and the nitrosativestress biomarker inducible nitric oxide synthase (iNOS), as well as the apoptosis biomarker tumour suppressor p53 in pathologicaltions.cond Therefore, we tested the hypothesis that acute pancreatitis can cause the pancreatic AMPK-iNOS-p53 axis to become dysregulated,and the inducer of AMPK, the hypoglycemic, anti-inflammatory, and antioxidant drug metformin, can ameliorate the disease. Intudy, this s acute pancreatitis was induced in rats using two injections of L-arginine (2.5 gm/kg) and culled after two days. The secondup gro (protective group) was pretreated for two weeks with 50 mg/kg metformin prior to the induction of acute pancreatitis and kept o metformin until sacrificed with other groups. Pancreatic injuries developed in the model group (L-arginine) demonstrated by a substantial increase in iNOS and p53 immunostaining, as well as biomarkers of pancreatic injury, and AMPK inhibition. All these investigated signaling molecules were significantly (p<0.001) modulated by metformin. In addition, a significant correlation was detectedtween be iNOS and AMPK, p53, as well as biomarkers of acute pancreatitis (amylase, lactate dehydrogenase, and myeloperoxidase). eseThus, th findings demonstrate an association between acute pancreatitis and the modulation of the pancreatic AMPK-iNOS-p53 axising while be protected by metformin.