Document Detail

Role of leukocytes in indomethacin-induced small bowel injury in the rat.
MedLine Citation:
PMID:  8141297     Owner:  NLM     Status:  MEDLINE    
This study assesses the role of neutrophils in indomethacin-induced small bowel injury and determines the influence of intestinal pH on the magnitude of this injury. Rat jejunum was perfused via the lumen with buffer, and mucosal injury was assessed by blood-to-lumen clearance of 51Cr-EDTA and quantitative histology. Reduction in luminal pH from 7.4 to 6.0 in the presence of indomethacin (1.0 mg/ml) increased 51Cr-EDTA clearance from 2.0 +/- 0.1 to 6.5 +/- 0.3 microliter.min-1.g-1. Indomethacin caused a reduction in villus length, an increase in villus width, and an increase in lesion score. Depletion of neutrophils with antiserum largely prevented the increase in 51Cr-EDTA clearance and morphological changes. Intravenous indomethacin given at a dose to mimic therapeutic plasma levels (1 mg/kg iv) had no significant effect on 51Cr-EDTA clearance but caused similar morphological changes to those observed following intraluminal administration. The data suggest that neutrophils play a role in acute indomethacin injury and that the drug given intravenously can cause morphological changes without necessarily altering mucosal permeability to 51Cr-EDTA.
H M Chmaisse; J S Antoon; P R Kvietys; M B Grisham; M A Perry
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  266     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-04-28     Completed Date:  1994-04-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  G239-46     Citation Subset:  IM    
School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
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MeSH Terms
Blood Pressure / drug effects
Edetic Acid / pharmacokinetics
Indomethacin / administration & dosage,  pharmacology*
Injections, Intravenous
Intestinal Mucosa / metabolism
Intestine, Small / drug effects*,  pathology*
Jejunum / metabolism
Leukocytes / physiology*
Rats, Wistar
Reg. No./Substance:
53-86-1/Indomethacin; 60-00-4/Edetic Acid

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

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