Intimal Hyperplasia in Rats after Subcutaneous Injection of a Somatostatin Analog

Author:

Wells Monique Y.1,Voute Hélène2,Lonchampt Marie-Odile3,Fisch Cécile3,Boulifard Virginie3,Picaut Philippe3

Affiliation:

1. Toxicology/Pathology Services Inc., Houston, Texas, USA and Paris, France

2. MDS Pharma, Saint Germain sur l’Arbresle, France

3. Ipsen, Les Ulis, France

Abstract

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.

Publisher

SAGE Publications

Subject

Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine

Cited by 4 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Cardiac, Vascular, and Skeletal Muscle Systems;Haschek and Rousseaux's Handbook of Toxicologic Pathology;2013

2. Cardiovascular System;Histopathology of Preclinical Toxicity Studies;2012

3. Data Analysis, Report Writing, and Regulatory Documentation;Pharmaceutical Toxicology in Practice;2011-05-13

4. Histomorphology and Vascular Lesions in Dorsal Rat Skin Used as Injection Sites for a Subcutaneous Toxicity Study;Toxicologic Pathology;2010-01-25

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