Early failure of intestinal barrier function and endotoxemia in severe acute pancreatitis

1998 ◽  
Vol 114 ◽  
pp. A1375 ◽  
Author(s):  
BJ Ammori ◽  
PG Leeder ◽  
RFG King ◽  
GR Barclay ◽  
IG Martin ◽  
...  
Author(s):  
Chengjiang Qiu ◽  
Kairui Liu ◽  
Xuguang Li ◽  
Weirun Chen ◽  
Sheng Zhang ◽  
...  

Background: The pathogenesis of severe acute pancreatitis (SAP) is mediated substantially by dysfunctions in the intestinal barrier. Euphorbia kansui (EK) is a medicinal plant used widely in traditional Chinese medicine to treat inflammation; however, its efficacy and mechanism of action in SAP treatment is not yet well understood. Objective: To investigate the role of EK in intestinal barrier tissue repair and in the pathogenesis and development of SAP. Methods: The rat SAP model was established by a retrograde injection of sodium taurocholate into the pancreatic bile duct. The SAP model group and the SAP + EK treatment groups were divided into 6 subgroups according to timing: 2, 6, 12, 24, 48, or 72 h after inducing SAP. The progression of the SAP rats and of the rats receiving the EK treatment was evaluated using the ascites volume, serum amylase and plasma endotoxin levels, and histological grading of intestinal mucosal damage. In addition, serum inflammatory factor contents were measured using enzyme-linked immunosorbent assay (ELISA) tests and apoptotic cells in damaged ileum tissue were detected using TUNEL staining. Apoptosis markers and other signaling proteins in intestinal mucosal cells were detected by immunohistochemical assays and then validated by combining these data with quantitative polymerase chain reactions and western blotting. Results: Compared with the results of the SAP model rats, the results of the rats that received EK treatment demonstrated that EK could effectively reduce the ascites volume and serum amylase and plasma endotoxin levels. EK treatment also greatly reduced the abnormal intestinal morphological alterations in the rat SAP model and significantly downregulated the serum contents of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. EK treatment inhibited the elevation of capapse-3, inhibited the decrease of the Bcl-2 protein, and decreased the number of apoptotic cells in rat ileum tissue. Finally, EK treatment abrogated the increase of HMGB1 and the suppression of MFG-E8 protein expression in the SAP + EK rat ileum tissue. Conclusion: EK suppresses SAP pathogenesis by restoring intestinal barrier function and modulating the HMGB1/MFG-E8 signaling axis.


2020 ◽  
Vol 20 (7) ◽  
pp. 566-577 ◽  
Author(s):  
Amlan Kumar Patra

Natural plant bioactive compounds (PBC) have recently been explored as feed additives to improve productivity, health and welfare of poultry following ban or restriction of in-feed antibiotic use. Depending upon the types of PBC, they possess antimicrobial, digestive enzyme secretion stimulation, antioxidant and many pharmacological properties, which are responsible for beneficial effects in poultry production. Moreover, they may also improve the intestinal barrier function and nutrient transport. In this review, the effects of different PBC on the barrier function, permeability of intestinal epithelia and their mechanism of actions are discussed, focusing on poultry feeding. Dietary PBC may regulate intestinal barrier function through several molecular mechanisms by interacting with different metabolic cascades and cellular transcription signals, which may then modulate expressions of genes and their proteins in the tight junction (e.g., claudins, occludin and junctional adhesion molecules), adherens junction (e.g., E-cadherin), other intercellular junctional proteins (e.g., zonula occludens and catenins), and regulatory proteins (e.g., kinases). Interactive effects of PBC on immunomodulation via expressions of several cytokines, chemokines, complement components, pattern recognition receptors and their transcription factors and cellular immune system, and alteration of mucin gene expressions and goblet cell abundances in the intestine may change barrier functions. The effects of PBC are not consistent among the studies depending upon the type and dose of PBC, physiological conditions and parts of the intestine in chickens. An effective concentration in diets and specific molecular mechanisms of PBC need to be elucidated to understand intestinal barrier functionality in a better way in poultry feeding.


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