The effects of p53 inhibition using pifithrin-α on acute necrotizing pancreatitis in rats

Abstract

To investigate the effects of p53 inhibition using pifithrin-\alpha (PFA) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The role of p53 during acute pancreatitis is unclear. Materials and methods: Rats were divided into 4 groups, 2 of which were initially given only saline (the sham group) and 2 of which were given glycodeoxycholic acid in order to induce ANP. Each group was then identified according to treatment plan: sham+saline, sham+PFA, ANP+saline, or ANP+PFA. The study then investigated the extent of acinar cell injury, apoptosis, mortality, systemic cardiorespiratory variables, functional capillary density (FCD), renal/hepatic functions, and changes in some enzyme markers for pancreatic and lung tissue during ANP in rats. Results: The induction of ANP resulted in a significant increase in mortality rate, pancreatic necrosis, apoptosis, serum activity of amylase, alanine aminotransferase (ALT), interleukin (IL)-6, lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, and tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung. In addition, ANP induction caused a significant decrease in concentrations of calcium, blood pressure, urine output, pO2, and functional capillary density (FCD). The use of PFA did not alter these changes. Conclusion: PFA demonstrated no effect on the course of ANP in rats. Therefore, it has no value in the treatment of acute pancreatitis.