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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Format: | Article |
Language: | English |
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Elsevier
1968-09-01
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Series: | Journal of Lipid Research |
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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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institution | Directory Open Access Journal |
issn | 0022-2275 |
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series | Journal of Lipid Research |
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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