sodium-taurodeoxycholate and Multiple-Organ-Failure

To investigate potential effects of ebselen and ethylhydroxyethyl cellulose (EHEC) on the acute phase responses and the severity of multiple organ dysfunction associated with acute pancreatitis.. Acute pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate. The increase of total protein content in the BALF was used as an indication for acute lung injury, plasma amylase for pancreatic damage, plasma bilirubin for acute liver dysfunction, and plasma creatinine for acute kidney dysfunction. Levels of interleukin (IL)-6, macrophage inflammatory protein (MIP)-2 in the BALF were determined by ELISA.. There was a dose-related tendency for ebselen or EHEC alone to prevent organ dysfunction and reduce elevated plasma levels of IL-6 and ICAM-1 expression on circulating leukocytes 12 h after AP induction. The combination of ebselen and EHEC significantly prevented pancreatitis-induced multiple organ injury, IL-6 production and ICAM-1 expression in rats and exhibited better effects than either monocompound alone.. The combination of ebselen and EHEC may be a new potential for treatment of acute severe pancreatitis.

Topics: Amylases; Animals; Anti-Inflammatory Agents, Non-Steroidal; Azoles; Bilirubin; Bronchoalveolar Lavage Fluid; Cellulose; Chemokine CXCL2; Chemokines, CXC; Creatine; Enteral Nutrition; Immunologic Factors; Intercellular Adhesion Molecule-1; Interleukin-6; Isoindoles; Male; Monocytes; Multiple Organ Failure; Organoselenium Compounds; Pancreatitis; Proteins; Rats; Rats, Sprague-Dawley; Taurodeoxycholic Acid

Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiology of acute conditions. The aim of the present study was to evaluate the role of activated tissue mast cells in the pathogenesis of multiple organ dysfunction syndrome following acute pancreatitis (AP).. AP was induced by the intraductal infusion of 5 per cent sodium taurodeoxycholate in the rat. Some 30 min before induction of AP, a mast cell stabilizer (sodium cromoglycate (SCG)) or antihistamines (pyrilamine, cyproheptadine, meclizine and amitriptyline) were administered intra peritoneally. Plasma exudation of radiolabelled albumin, histamine, myeloperoxidase (MPO), monocyte chemoattractant protein (MCP) 1 and adhesion molecules (platelet endothelial cell adhesion molecule (PECAM) 1 and L-selectin) were measured.. The mast cell stabilizer significantly reduced plasma exudation in the pancreas, colon and lungs (P < 0.05), decreased the release of histamine at 1 h (P < 0.05), and reduced MPO activity and MCP-1 levels in the colon and lungs (P < 0.05) but not in the pancreas. Expression of PECAM-1 and L-selectin on total circulating leucocytes in rats with AP and SCG pretreatment did not differ from that in sham controls, while levels in animals that had AP and saline pretreatment were half of those seen following sham operation.. Activation of mast cells after induction of AP is involved in the development of endothelial barrier dysfunction in both the pancreas and extrapancreatic organs/tissues, particularly in the lungs and colon. This may, at least partly, contribute to the sequential development of multiple organ dysfunction and organ/tissue-specific endothelial barrier dysfunction.

Topics: Acute Disease; Animals; Chemokine CCL2; Endothelium, Vascular; Flow Cytometry; Histamine; L-Selectin; Leukocytes; Male; Mast Cells; Multiple Organ Failure; Pancreas; Pancreatitis; Peroxidase; Platelet Endothelial Cell Adhesion Molecule-1; Random Allocation; Rats; Rats, Sprague-Dawley; Taurodeoxycholic Acid; Tumor Necrosis Factor-alpha