Document Detail


Corticosteroid pretreatment prevents small intestinal mucosal lesion induced by acetic acid-perfusion model in rats.
MedLine Citation:
PMID:  11258553     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One of the important problems in experimentally induced small intestinal lesions is that there is no reproducible model of diffuse and stable mucosal lesion. In this paper, we studied in detail the effects of continuous perfusion of various concentrations of acetic acid on the rat small intestinal mucosa. In order to evaluate its applicability for screening of the preventive effect of drugs on gut damage, we also evaluated the efficacy of corticosteroid pretreatment in preventing acetic acid-induced mucosal lesion. Male Sprague-Dawley rats were fasted for 12 hr, and the small intestinal lumen was perfused with 1%, 1.5%, 2.5%, 3%, 3.75% (pH 2.4-2.6) acetic acid or saline (control) at 1 ml/min for 15 min. In separate experiments, the effect of preadministration of budesonide (0.5 or 0.75 mg/kg/day) and prednisone (0.75 mg/kg/day) on 1.5% acetic acid-induced mucosal damage was investigated. Macroscopic and microscopic lesions occurred diffusely in a concentration-dependent fashion. Histological findings revealed signs of transmural inflammation characterized by mucosal-submucosal edema, ulceration, and neutrophil infiltration. Mucosal-submucosal height had an inverse relation with the acetic acid concentrations perfused. Myeloperoxidase activity levels increased several-fold in the acetic acid-perfused groups. Corticosteroid pretreatment prevented microscopic damage and was associated with reduction of MPO activity levels in 1.5% acetic acid-perfused rats. We conclude that this simple and reproducible model could be applied for the screening of new drugs in the gastrointestinal tract in which large numbers of animals are taken into account.
Authors:
I Pacheco; M Otaka; M Jin; H Sasahara; A Iwabuchi; M Odashima; N Konishi; I Wada; O Masamune; S Watanabe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Digestive diseases and sciences     Volume:  45     ISSN:  0163-2116     ISO Abbreviation:  Dig. Dis. Sci.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-03-21     Completed Date:  2001-04-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902782     Medline TA:  Dig Dis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2337-46     Citation Subset:  AIM; IM    
Affiliation:
First Department of Internal Medicine, Akita University School of Medicine, Akita City, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acetic Acid / pharmacology*
Animals
Anti-Inflammatory Agents / pharmacology*
Budesonide / pharmacology*
Drug Evaluation, Preclinical / methods
Intestinal Mucosa / drug effects*,  enzymology,  pathology
Intestine, Small / drug effects*,  enzymology,  pathology
Male
Models, Animal
Perfusion
Peroxidase / metabolism
Prednisone / pharmacology*
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 51333-22-3/Budesonide; 53-03-2/Prednisone; 64-19-7/Acetic Acid; EC 1.11.1.7/Peroxidase

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


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