Effect of long-term administration of AY-9944, an inhibitor of 7-dehydrocholesterol Δ7-reductase, on serum and tissue lipids in the rat

The effect of long-term administration of AY-9944, a specific inhibitor of cholesterol biosynthesis, was examined in rats maintained on diets with low and high cholesterol and fat content. Sterol and phospholipid levels were determined in the serum, liver, adrenals, lungs, and brain after 6 and 12 m...

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Main Authors: D. Dvornik, P. Hill
Format: Article
Language:English
Published: Elsevier 1968-09-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S002222752042704X
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author D. Dvornik
P. Hill
author_facet D. Dvornik
P. Hill
author_sort D. Dvornik
collection DOAJ
description The effect of long-term administration of AY-9944, a specific inhibitor of cholesterol biosynthesis, was examined in rats maintained on diets with low and high cholesterol and fat content. Sterol and phospholipid levels were determined in the serum, liver, adrenals, lungs, and brain after 6 and 12 months of feeding AY-9944 at several dose levels.In all the tissues examined, the cholesterol content was lowered and the cholesterol was partly replaced by 7-dehydrocholesterol biosynthesized instead of cholesterol in the presence of AY-9944. Cholesterol levels were particularly low in the serum and adrenals, while 7-dehydrocholesterol accumulated in the lungs. The fall in cholesterol and appearance of 7-dehydrocholesterol were reversible. Alterations of this type in the brain indicated that sterol metabolism is active in the adult rat brain. Addition of cholesterol to the diet reduced the effect of the inhibitor by eliminating the liver as a site of sterol synthesis.
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spelling doaj.art-87d5904cd28e4d7aa9e1f076291f5c2b2022-12-21T21:24:13ZengElsevierJournal of Lipid Research0022-22751968-09-0195587595Effect of long-term administration of AY-9944, an inhibitor of 7-dehydrocholesterol Δ7-reductase, on serum and tissue lipids in the ratD. Dvornik0P. Hill1Department of Biochemistry, Ayerst Research Laboratories, Montreal, CanadaDepartment of Biochemistry, Ayerst Research Laboratories, Montreal, CanadaThe effect of long-term administration of AY-9944, a specific inhibitor of cholesterol biosynthesis, was examined in rats maintained on diets with low and high cholesterol and fat content. Sterol and phospholipid levels were determined in the serum, liver, adrenals, lungs, and brain after 6 and 12 months of feeding AY-9944 at several dose levels.In all the tissues examined, the cholesterol content was lowered and the cholesterol was partly replaced by 7-dehydrocholesterol biosynthesized instead of cholesterol in the presence of AY-9944. Cholesterol levels were particularly low in the serum and adrenals, while 7-dehydrocholesterol accumulated in the lungs. The fall in cholesterol and appearance of 7-dehydrocholesterol were reversible. Alterations of this type in the brain indicated that sterol metabolism is active in the adult rat brain. Addition of cholesterol to the diet reduced the effect of the inhibitor by eliminating the liver as a site of sterol synthesis.http://www.sciencedirect.com/science/article/pii/S002222752042704Xratcholesterol biosynthesisinhibition7-dehydrocholesterol Δ7-reductasecholesterol lowering7-dehydrocholesterol accumulation
spellingShingle D. Dvornik
P. Hill
Effect of long-term administration of AY-9944, an inhibitor of 7-dehydrocholesterol Δ7-reductase, on serum and tissue lipids in the rat
Journal of Lipid Research
rat
cholesterol biosynthesis
inhibition
7-dehydrocholesterol Δ7-reductase
cholesterol lowering
7-dehydrocholesterol accumulation
title Effect of long-term administration of AY-9944, an inhibitor of 7-dehydrocholesterol Δ7-reductase, on serum and tissue lipids in the rat
title_full Effect of long-term administration of AY-9944, an inhibitor of 7-dehydrocholesterol Δ7-reductase, on serum and tissue lipids in the rat
title_fullStr Effect of long-term administration of AY-9944, an inhibitor of 7-dehydrocholesterol Δ7-reductase, on serum and tissue lipids in the rat
title_full_unstemmed Effect of long-term administration of AY-9944, an inhibitor of 7-dehydrocholesterol Δ7-reductase, on serum and tissue lipids in the rat
title_short Effect of long-term administration of AY-9944, an inhibitor of 7-dehydrocholesterol Δ7-reductase, on serum and tissue lipids in the rat
title_sort effect of long term administration of ay 9944 an inhibitor of 7 dehydrocholesterol δ7 reductase on serum and tissue lipids in the rat
topic rat
cholesterol biosynthesis
inhibition
7-dehydrocholesterol Δ7-reductase
cholesterol lowering
7-dehydrocholesterol accumulation
url http://www.sciencedirect.com/science/article/pii/S002222752042704X
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