The Studies On Preventive And Therapeutic Effects Of Curcumin In Taurocholate-Induced Pancreatitis

Acute pancreatitis is an important clinical problem, and the incidence has been increasing. Acute pancreatitis is mild and self-limiting in most patients; however, it is severe in about 25% of patients, and nearly 50% of these will die because of complications of the disease. Specific and effective therapies are lacking, and advances in treatment have been difficult because of a lack of understanding of the early cellular events important in the pathophysiology of this disease.Recent data indicate that the inflammatory response is initiated by injured pancreatic acinar cells that produce inflammatory mediators, such as cytokines and adhesion molecules, ultimately leading to systemic complications. NFB is just the upstream "master regulators" of these molecules. NFB activation, at least in part, regulates the expression of the molecules, all of which are upregulated in pancreatitis. So therapeutic strategies should be aimed at the capital regulator of inflammation.Inhibiting NFicB activation should alleviate inflammation not only in the pancreas but also in distant organs affected during pancreatitis. Recent studies indicate that the bioflavonoid curcumin could inhibit NFB activation. Of importance, curcumin is not toxic and can be administered in large quantities.The purpose of this study was to investigate the role of NFicB in acute pancreatitis induced with retrograde injection of taurocholate, and to identify whether curcumin could inhibit the inflammatory response and significantly ameliorate pancreatitis in this model.1. Induction of experimental pancreatitis in the rat10Acute pancreatitis was induced according to Aho HJ et al. Sodium taurocholate solution (4% or 1%) retrogradely injected into the pancreatic duct system of the rat caused acute hemorrhagic and necrotizing pancreatitis (AHNP) or acute edematous pancreatitis (AEP). The pancreatic lesions were characterized by interstitial oedema, acinar cell vacuolization and infiltration of inflammatory cell in AEP rat. And interstitial oedema, extensive necrotic changes of the acinar cells, and haemorrhages were characterization of AHNP. This study has shown that the presence of sodium taurocholate, a bile salt, within the duct system of rat pancreas can initiate a disease with gross and histopathological changes that correspond to those seen in human acute pancreatitis. The present experimental model is suitable for the next studies.2. NFB activation in rat pancreas is an early event associated with taurocholate-induced edematous pancreatitisTranscription factor nuclear factor- (NF-KB) is activated in cerulein pancreatitis and mediates cytokine expression. The role of transcription factor activation in other models of mild pancreatitis has not been established. Here we report upregulation of NF-KB and inflammatory molecules, and their correlation with local pancreatic injury, in a model of edematous pancreatitis. Rats received intraductal infusion of taurocholate (1%) or saline. NF-KB activation were assessed by electrophoretic mobility shift assay, protein expression of IicBa and IB was assessed by Western blot and immunofluorescence, and rnRNA expression of interleukin-lp, interleukin-6, tumor necrosis factor-a, Groa, monocyte chemoattractant protein-1, and inducible nitric oxide synthase was assessed by semiquantitative RT-PCR. Immunofluorescence was used to identify the source of NF-KB P65. The severity of the disease was measured by a number of parameters (histology, water content, serum amylase, myeloperoxidase activity, and pancreatic trypsin). NF-icB was strongly activated in the pancreas within 30 min oftaurocholate infusion; a second phase of NF-KB activation was prominent at113-12 h. This biphasic kinetics could result from observed transient degradation of the inhibitory protein IB and slower but sustained degradation of lKBp\ mRNA of MCP-1 and Gro-a appeared to be obviously induced in this model. Saline infusion mildly affected these parameters. N-acetylcysteine (NAC) blocked ?NF-B activation and significantly improved parame...