Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-11-16
pubmed:abstractText
EP2306 [2-(4-biphenyl)-4-methyl-octahydro-1,4-benzoxazin-2-ol, hydrobromide] inhibits squalene synthase and lipid biosynthesis and possesses antioxidant properties. We hypothesized that EP2306 can effectively modify circulating lipids and reduce atherosclerosis in the cholesterol-fed rabbit. Animals were fed a high-cholesterol diet for 4 weeks followed by 4 (phase 1 and 2) or 12 weeks (phase 3) of drug treatment while on high-cholesterol diet. In phase 1, the dose-effect relationship of EP2306 on lipids and atherosclerosis was established, and its most effective dose was determined (2 mg/kg). This dose reduced significantly total cholesterol (512 +/- 96 mg/dl before versus 320 +/- 124 mg/dl after treatment, p < 0.05) and atherosclerotic lesions compared with control animals. In phase 2, the effects of 2 mg/kg EP2306, 2.5 mg/kg simvastatin, and their combination were assessed. Although no significant effect on lipid parameters was observed, there was a significant reduction (35 +/- 5%, p < 0.05) of atherosclerotic lesions in animals treated with EP2306, a similar reduction with simvastatin, and a further reduction (48 +/- 7%, p < 0.05) when the two agents were combined. In animals treated for 12 weeks with the drugs (phase 3), only EP2306 significantly reduced atherosclerotic lesions by more than 50%, whereas simvastatin alone or in combination with EP2306 had no effect. Treatment with EP2306 did not adversely affect liver transaminases or cause any histopathological changes on various organs of the animals. In conclusion, we have shown that EP2306 inhibits atherosclerosis in vivo, indicating potential as a novel therapeutic agent for coronary artery disease and other atherosclerosis-related disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
323
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
794-804
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
EP2306 [2-(4-biphenyl)-4-methyl-octahydro-1,4-benzoxazin-2-ol, hydrobromide], a novel squalene synthase inhibitor, reduces atherosclerosis in the cholesterol-fed rabbit.
pubmed:affiliation
Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't