Pharmacological Targeting of the Inflamed Intestinal Barrier

2016 ◽  
Vol 22 (35) ◽  
pp. 5400-5414 ◽  
Author(s):  
Attila Farkas ◽  
Asma Nusrat
Keyword(s):  
Intestinal Barrier

Iron and Malaria: Absorption, Efficacy and Safety

2010 ◽  
Vol 80 (45) ◽  
pp. 279-292 ◽  
Author(s):  
Richard Hurrell
Keyword(s):  
Pathogenic Bacteria ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Malarial Parasite ◽  
Asymptomatic Malaria ◽  
Iron Supplements ◽  
Fortified Food ◽  
Care Giving ◽  
Single Meal ◽  
Women And Children

Febrile malaria and asymptomatic malaria parasitemia substantially decrease iron absorption in single-meal, stable isotope studies in women and children, but to date there is no evidence of decreased efficacy of iron-fortified foods in malaria-endemic regions. Without inadequate malarial surveillance or health care, giving iron supplements to children in areas of high transmission could increase morbidity and mortality. The most likely explanation is the appearance of non-transferrin-bound iron (NTBI) in the plasma. NTBI forms when the rate of iron influx into the plasma exceeds the rate of iron binding to transferrin. Two studies in women have reported substantially increased NTBI with the ingestion of iron supplements. Our studies confirm this, but found no significant increase in NTBI on consumption of iron-fortified food. It seems likely that the malarial parasite in hepatocytes can utilize NTBI, but it cannot do so in infected erythrocytes. NTBI however may increase the sequestration of parasite-infected erythrocytes in capillaries. Bacteremia is common in children with severe malaria and sequestration in villi capillaries could lead to a breaching of the intestinal barrier, allowing the passage of pathogenic bacteria into the systemic circulation. This is especially important as frequent high iron doses increase the number of pathogens in the intestine at the expense of the barrier bacteria.

Restoration of intestinal mucosal in Euphorbia kansui-treated severe acute pancreatitis rats is based on HMGB1/MFG-E8 expression

2020 ◽  
Vol 21 ◽  
Author(s):  
Chengjiang Qiu ◽  
Kairui Liu ◽  
Xuguang Li ◽  
Weirun Chen ◽  
Sheng Zhang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Serum Amylase ◽  
Intestinal Barrier ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Factor ◽  
Apoptotic Cells ◽  
Rat Ileum ◽  
Plasma Endotoxin ◽  
Euphorbia Kansui

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.

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