Alterations in intestinal function in acute pancreatitis in an experimental model

Abstract

Gastrointestinal tract failure may be involved in the development of systemic septic complications in acute pancreatitis. Systemic and intestinal circulation, intestinal permeability and absorptive function were evaluated in the early course of acute pancreatitis induced in rats by retrograde intraductal injection of 0.2 ml of 5 per cent sodium taurodeoxycholate and 0.4 nmol trypsin. A decrease in systemic arterial pressure and intestinal blood flow and an increase in intestinal permeability as measured by the leakage of 125I-labelled human serum albumin from blood to lumen were noted in the distal ileum and colon, reaching statistically significant differences 6 h after induction of pancreatitis. The transport of small molecular markers (sodium fluorescein and 51Cr-labelled ethylenediamine tetra-acetic acid) through the distal ileum and colon in vitro from the mucosal to the serosal site in Ussing chambers significantly increased in the early periodic (20-60 min) of incubation, while the passage of a macromolecular marker (ovalbumin) demonstrated a definite increase at 60-120 min of incubation. D-Xylose absorption from the gut lumen to the portal vein was significantly less in acute pancreatitis than after sham operation. Intravenous administration of the hydroxyl radical scavenger dimethylsulphoxide prevented the compromised intestinal permeability and gut absorptive capacity induced by acute pancreatitis, but did not affect the reduced arterial pressure and intestinal microcirculation. Cytotoxic oxygen-derived free radicals may contribute to the development of alterations in intestinal permeability and absorptive function found in the early stage of acute pancreatitis in the rat.

Potential role of reactive oxygen species in pancreatitis-associated multiple organ dysfunction

“…Intravenous administration of the hydroxyl radical scavenger dimethylsulphoxide prevented the compromised intestinal permeability and gut-absorptive capacity induced by acute pancreatitis, but did not affect the reduced arterial pressure and intestinal microcirculation [73] . Cytotoxic oxygen-derived free radicals contribute to the development of alterations in intestinal permeability and absorptive function found in the early stage of acute pancreatitis in the rat [73] .…”

“…Cytotoxic oxygen-derived free radicals contribute to the development of alterations in intestinal permeability and absorptive function found in the early stage of acute pancreatitis in the rat [73] . Dimethylsulphoxide does not act as a plasma expander to protect against mucosal injury by increasing the circulatory volume, and reduced intestinal blood fl ow by itself does not seem to be a primary factor directly affecting gut permeability and absorption [73] . A possible mechanism to explain failure of the intestinal barrier in experimental acute pancreatitis is that systemic and local ischemia-reperfusion injury reduces the mucosal microcirculation, compromises oxygen delivery and results in insuffi cient energy production.…”

“…Excessive production of oxygen-derived free radicals can induce alterations in intestinal permeability and absorption in acute pancreatitis by effects of lysosomal proteases and eicosanoids released by stimulated leukocytes, macrophages, dendritic cells and antigen-presenting cells in the mucosa, and by lipid peroxidation of cell membranes [75] . Extrapancreatic endothelial barrier dysfunction characterized by increased microcirculatory endothelial permeability has been noted in the early stage of acute pancreatitis [23,70,73] . High concentrations of ROS generated in the early stage of pancreatitis are responsible for such an increase in endothelial permeability by promoting expression and activation of adhesion molecules on both leukocytes and endothelial cells, leading to alterations in cell signal transduction and redox-regulated transcription factors such as activator protein-1 and NF-B.…”

Bacterial Infection of Pancreatic Necrosis: Role of Bacterial Translocation, Impact of Antibiotic Treatment

“…Mucosal barrier damage during acute pancreatitis leads to an increase in permeability [29,33] which facilitates the escape of bacteria from the gastrointestinal lumen. The mechanisms responsible for this finding re-Isenmann/Beger main unclear.…”

“…The mechanisms responsible for this finding re-Isenmann/Beger main unclear. Impaired colonic mucosal and serosal blood supply has been found during the early stages of acute pancreatitis and seem to be one of the factors contributing to these changes [33,34]. Additionally, it has been speculated that release of excessive amounts of inflammatory mediators leads to failure of the intestinal barrier [35].…”