Time response of cholesterol synthesis inhibition by compactin-related compounds. In vitro quantitation of the "escape phenomenon".

Abstract

The time course of the inhibition of cholesterol synthesis by low and high doses of mevinolin and monacolin X were studied in normal human skin fibroblasts, fibroblasts without low density lipoprotein receptor and HepG2 hepatoma cells. Low doses of the inhibitors (0.2 ng/mL) caused a sharp decrease in the rate of cholesterol synthesis during the first 2-3 h, which gradually increased to about 40% during the next 6 h. Further incubation led to a decrease or stabilization of the cholesterol synthesis rate. High doses of the drugs (100 mg/mL) strongly inhibited cholesterol synthesis during the first 2-3 h, followed by a moderate increase during the next 20 h. No drug or tissue selectivity was observed.

• Authors: D D Sviridov, A Endo, M Y Pavlov, V S Repin
• Journal: Lipids (Lipids) Vol. 28 Issue 6 Pg. 569-71 (Jun 1993) ISSN: 0024-4201 [Print] United States
• PMID: 8355584 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anticholesteremic Agents
• Naphthalenes
• monacolin X
• Cholesterol
• Lovastatin

Topics

• Anticholesteremic Agents (pharmacology)
• Cholesterol (biosynthesis)
• Dose-Response Relationship, Drug
• Fibroblasts (drug effects, metabolism)
• Humans
• Hyperlipoproteinemia Type II (metabolism)
• Lovastatin (pharmacology)
• Naphthalenes (pharmacology)
• Skin (metabolism)
• Tumor Cells, Cultured (drug effects, metabolism)