Document Detail


HL-004, the ACAT inhibitor, prevents the progression of atherosclerosis in cholesterol-fed rabbits.
MedLine Citation:
PMID:  9519807     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HL-004, N-(2,6-diisopropylphenyl) tetradecylthioacetamide, a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, was evaluated concerning the possible prevention of hyperlipidemia and atherosclerosis in 1% cholesterol-fed rabbits. HL-004 (0.2, 5 and 25 mg/kg) was orally administered once a day for 12 weeks. HL-004 inhibited the rise of total serum cholesterol at a dose of 5 mg/kg and over. In the thoracic aorta, HL-004 at the doses of 5 mg/kg and 25 mg/kg reduced the total cholesterol content by 56.3% and 84.2% compared with control, and decreased ACAT activity, dose-dependently. HL-004 also attenuated the development of aortic lesions. The area of atherosclerotic lesions was reduced by 30.3% with 5 mg/kg of HL-004 and 100% with 25 mg/kg. In this study, we suggest that the main reason for HL-004 preventing the progression of atherosclerosis is its hypocholesterolemic effect due to the inhibition of cholesterol absorption in the intestine.
Authors:
Y Asami; I Yamagishi; S Murakami; H Araki; K Tsuchida; S Higuchi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  62     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  1998  
Date Detail:
Created Date:  1998-04-02     Completed Date:  1998-04-02     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1055-63     Citation Subset:  IM    
Affiliation:
Research Laboratories, Taisho Pharmaceutical Co. Ltd., Ohmiya, Saitama, Japan. S10960@ccam.taisho.co.jp
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MeSH Terms
Descriptor/Qualifier:
Acetanilides / therapeutic use*
Animals
Anticholesteremic Agents / therapeutic use*
Aorta, Thoracic / metabolism
Arteriosclerosis / etiology,  prevention & control*
Body Weight / drug effects
Cholesterol / blood
Cholesterol, Dietary / adverse effects*
Disease Progression
Eating / drug effects
Enzyme Inhibitors / therapeutic use*
Lipids / blood
Liver / metabolism
Male
Rabbits
Sterol O-Acyltransferase / antagonists & inhibitors*,  metabolism
Chemical
Reg. No./Substance:
0/Acetanilides; 0/Anticholesteremic Agents; 0/Cholesterol, Dietary; 0/Enzyme Inhibitors; 0/HL 004; 0/Lipids; 57-88-5/Cholesterol; EC 2.3.1.26/Sterol O-Acyltransferase

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


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