February 1993
Volume 34, Issue 2
Free
Articles  |   February 1993
Pravastatin and simvastatin differently inhibit cholesterol biosynthesis in human lens.
Author Affiliations
  • A C de Vries
    TNO Institute of Ageing and Vascular Research (IVVO-TNO), Gaubius Laboratory, Leiden, The Netherlands.
  • M A Vermeer
    TNO Institute of Ageing and Vascular Research (IVVO-TNO), Gaubius Laboratory, Leiden, The Netherlands.
  • H Bloemendal
    TNO Institute of Ageing and Vascular Research (IVVO-TNO), Gaubius Laboratory, Leiden, The Netherlands.
  • L H Cohen
    TNO Institute of Ageing and Vascular Research (IVVO-TNO), Gaubius Laboratory, Leiden, The Netherlands.
Investigative Ophthalmology & Visual Science February 1993, Vol.34, 377-384. doi:
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      A C de Vries, M A Vermeer, H Bloemendal, L H Cohen; Pravastatin and simvastatin differently inhibit cholesterol biosynthesis in human lens.. Invest. Ophthalmol. Vis. Sci. 1993;34(2):377-384.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
This content is PDF only. Please click on the PDF icon to access.
Abstract

PURPOSE: In the current study, the hypocholesterolemic drugs pravastatin and simvastatin were compared for their influence on cholesterol biosynthesis in the human lens. METHODS: For measurements of cholesterol and fatty acid synthesis rates, human lenses were incubated for 20 hr in the presence of [14C]-acetate, and pravastatin or simvastatin. Radiolabeled [14C]-cholesterol and [14C]-fatty acids were determined. To avoid the influence of individual differences, one lens from each donor was incubated without drug (control) and the other lens was incubated in the presence of drug. For each lens pair, the percentage inhibition of the cholesterol synthesis caused by the drug was calculated. Fatty acid synthesis was not influenced by the drugs. By comparing the fatty acid synthesis rate of the drug-incubated with the control lens of a pair, a predefined exclusion criterion was used to eliminate lens pairs in which the lenses had no comparable biosynthetic capacities. RESULTS: Using various concentrations of the drugs, a dose-response curve was constructed for the inhibition of the cholesterol synthesis. The IC50 values (drug concentration give 50% inhibition) were 0.5 mumol/l and 0.004 mumol/l for pravastatin and simvastatin, respectively. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity in microsomal membranes from human lens cortex was inhibited by simvastatin and pravastatin to the same extent. CONCLUSIONS: Under the conditions used in this study, cholesterol synthesis in human lenses is inhibited by simvastatin 100-fold more effectively than by pravastatin. This difference was likely due to differences in the intracellular exposure of the reductase to the drugs in intact human lenses.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×