PMID: 2505850Sep 11, 1989Paper

Effect of CS-514, a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase, on cholesterol gallstone formation in hamsters

Biochimica Et Biophysica Acta
K KoideG Kajiyama

Abstract

Male golden hamsters fed a glucose diet as a model for cholesterol gallstone formation were used to investigate the effect of CS-514 on the lithogenicity of bile. Treatment with 0.05% (w/w) CS-514 in the diet for 1-4 weeks caused a decrease in plasma cholesterol and triacylglycerol levels. A marked increase in hepatic hydroxymethylglutaryl-CoA reductase activity in vitro and also an increased de novo cholesterol synthesis in the liver were induced by treatment with CS-514 for 1-4 weeks. The concentration of free cholesterol in liver microsomes and the cholesterol 7 alpha-hydroxylase activity were both decreased by treatment with CS-514 for 1 week, but were not affected by treatment for 4 weeks. The cholesterol output into bile and the lithogenic index of bile were double those of the control (glucose diet only) following treatment with CS-514 for 4 weeks, and the subsequent incidence of cholesterol gallstone formation was elevated. The content of free cholesterol and cholesterol ester in the liver was not affected by treatment with CS-514 for 4 weeks. These results suggest that long-term treatment with CS-514 causes a compensatory increase in the synthesis of hydroxymethylglutaryl-CoA reductase which leads to augmented hepatic ...Continue Reading

References

Sep 1, 1988·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·W C DuaneR L Gebhard
Mar 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·D K SpadyJ M Dietschy
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May 1, 1968·The Journal of Clinical Investigation·W H Admirand, D M Small
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Jan 1, 1952·Acta Pathologica Et Microbiologica Scandinavica·H DAM, F CHRISTENSEN

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Citations

Dec 25, 2002·Biological & Pharmaceutical Bulletin·Masae SawadaJiro Seki

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