The therapeutic effect of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine in mice with acute necrotizing pancreatitis

Abstract

To investigate the therapeutic effect of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OXPAPC) in animal model of acute necrotizing pancreatitis (ANP) and its possible mechanism. Forty-eight C57BL/6J mice were randomly divided into two groups, ANP group and ANP treated with OXPAPC group. ANP model was induced by seven times administration of cerulein (50 microg/kg) challenged by lipopolysaccharide (LPS) (5 mg/kg) intraperitoneal injection. Treatment with OXPAPC was started 5 mins before LPS injection. At the 9th hour, 12nd hour and 24th hour after the first injection of cerulein, serum levels of amylase and lactate dehydrogenase (LDH) were measured. Severity of pancreatitis was evaluated by histological scoring system. The activity of myeloperoxidase (MPO) in pancreas was determined by zymohistochemistry. Intrapancreatic TNF-alpha, IL-1beta, ICAM-1 and E-selectin mRNA expressions in pancreas were studied by semi-quantitative RT-PCR. The activation of nuclear factor kappaB (NF-kappaB) and c-Jun-N-terminal kinase 1 (JNK1) were investigated by the methods of western blot. Treatment with OXPAPC significantly decreased serum amylase and LDH levels at the 9th hr and 12nd hour. Histologically, OXPAPC reduced the severity of pancreatic injury including inflammatory cell infiltration and necrosis at 12nd hour and 24th hour. There was a significant decrease of MPO activity in OXPAPC group as compared to ANP group. Intrapancreatic TNF-alpha, IL-1beta, ICAM-1 and E-selectin mRNA levels were reduced in OXPAPC-treated group. Western blot showed down-regulation of NF-KappaB p65 and JNK1 expression were found in OXPAPC-treated mice. OXPAPC decreased the severity of experimental acute pancreatitis in mice and inhibited the intrapancreatic inflammatory mediators expression in vivo. The protective effect of OXPAPC was mediated, at least in part, through blocking endotoxin signal pathway.