Document Detail


Intimal hyperplasia in rats after subcutaneous injection of a somatostatin analog.
MedLine Citation:
PMID:  19188469     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The somatostatin analog octreotide was administered to male and female Sprague-Dawley rats by subcutaneous injection for thirteen weeks at 0 (saline control), 0 (placebo control [mannitol and lactic acid; pH 4.2]), 1.25 mg/kg/day and 2.5 mg/kg/day to explore its potential effect on cutaneous vascular morphology. The placebo caused an increase in the incidence of intimal hyperplasia compared to saline controls in female rats; octreotide increased the incidence and severity of intimal hyperplasia in males and females. Intimal hyperplasia consisted of increased numbers of cells located between the endothelial cell layer and the internal elastic lamina. Severity was based on the degree of compromise of the vascular lumen (regardless of vessel size and number), with severely affected vessels having no visible lumen. Intimal hyperplasia in rats treated with octreotide was considered to be an unexpected and adverse finding, given that this compound and other somatostatin analogs have been investigated as reducers of intimal proliferation or restenosis after angioplasty in humans and that no such lesion has been reported in the literature for this class of compound to date. The induction of intimal hyperplasia by the placebo is also a notable finding; this may be because of the low pH of the formulation.
Authors:
Monique Y Wells; Hélène Voute; Marie-Odile Lonchampt; Cécile Fisch; Virginie Boulifard; Philippe Picaut
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Publication Detail:
Type:  Journal Article     Date:  2009-02-02
Journal Detail:
Title:  Toxicologic pathology     Volume:  37     ISSN:  1533-1601     ISO Abbreviation:  Toxicol Pathol     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-03-31     Completed Date:  2009-06-16     Revised Date:  2012-01-05    
Medline Journal Info:
Nlm Unique ID:  7905907     Medline TA:  Toxicol Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  235-43     Citation Subset:  IM    
Affiliation:
Ipsen, Les Ulis, France. mywells@toxpath.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Dose-Response Relationship, Drug
Female
Hydrogen-Ion Concentration
Hyperplasia / chemically induced*,  pathology
Injections, Subcutaneous
Male
Models, Biological
Octreotide / administration & dosage,  pharmacology*
Rats
Rats, Sprague-Dawley
Somatostatin / administration & dosage,  analogs & derivatives*,  pharmacology*
Time Factors
Tunica Intima / drug effects*,  pathology
Chemical
Reg. No./Substance:
51110-01-1/Somatostatin; 83150-76-9/Octreotide

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


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