Document Detail


Severity of pancreatitis-associated gut barrier dysfunction is reduced following treatment with the PAF inhibitor lexipafant.
MedLine Citation:
PMID:  15826603     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of the present study was to investigate the potential effect of treatment with a platelet-activating factor (PAF) antagonist, lexipafant (BB-882), on gut endothelial and epithelial barrier dysfunction and leukocyte recruitment in rats with acute pancreatitis. Severe acute pancreatitis was induced by the intraductal administration of 5% sodium taurodeoxycholate and pancreatitis-associated gut barrier dysfunction was characterized by increased exudation of radiolabelled albumin into the interstitium and alterations in bidirectional (over both the endothelial and epithelial barrier components) permeability of the intestine at the early stage of bile salt-induced acute pancreatitis. Levels of interleukin 1beta and 6, ileal and colonic myeloperoxidase (MPO) content, clearance of radiolabelled albumin from blood to the gut lumen or gut lumen to blood, and leakage of radiolabelled albumin to the ileum or colon were measured 3 and 12h after induction of acute pancreatitis. Treatment with lexipafant 30 min and 6h after pancreatitis reduced severity of pancreatitis-associated intestinal dysfunction, associated with a diminish in systemic concentrations of IL-1 and local leukocyte recruitment. The findings imply that PAF plays a critical role in the development of pancreatitis-associated gut barrier dysfunction and that PAF antagonist in some forms may represent potential candidates for future therapeutic intervention.
Authors:
Per Leveau; Xiangdong Wang; Zhengwu Sun; Anna Börjesson; Ellen Andersson; Roland Andersson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  69     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-13     Completed Date:  2005-05-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1325-31     Citation Subset:  IM    
Affiliation:
Department of Surgery, Lund University Hospital, SE-22185 Lund, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Animals
Capillary Permeability / drug effects
Chromium Radioisotopes / metabolism
Endothelium, Vascular / physiopathology
Humans
Imidazoles / pharmacology*,  therapeutic use
Interleukin-1 / blood
Interleukin-6 / blood
Intestinal Mucosa / blood supply,  drug effects*,  metabolism*
Intestine, Small / blood supply*,  physiology
Iodine Radioisotopes / metabolism
Leucine / analogs & derivatives*,  pharmacology*,  therapeutic use
Leukocytes / drug effects
Male
Pancreatitis / blood,  chemically induced,  drug therapy*,  physiopathology
Peroxidase / blood,  drug effects
Platelet Activating Factor / antagonists & inhibitors*
Rats
Rats, Sprague-Dawley
Serum Albumin / pharmacokinetics
Taurodeoxycholic Acid
Chemical
Reg. No./Substance:
0/Chromium Radioisotopes; 0/Imidazoles; 0/Interleukin-1; 0/Interleukin-6; 0/Iodine Radioisotopes; 0/Platelet Activating Factor; 0/Serum Albumin; 139133-26-9/lexipafant; 516-50-7/Taurodeoxycholic Acid; 61-90-5/Leucine; EC 1.11.1.7/Peroxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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