Different effects of the hypolipidemic drugs pravastatin and lovastatin on the cholesterol biosynthesis of the human ocular lens in organ culture and on the cholesterol content of the rat lens in vivo

Abstract

This study aimed to investigate the influence of the hypocholesterolemic drugs pravastatin and lovastatin on the cholesterol biosynthesis in the ocular lens. Two model systems were used: a human lens organ culture system and an in vivo rat lens system. For measurements of cholesterol and fatty acid synthesis rates, human lenses were incubated for 20 h in the presence of [ 14C]acetate. Pravastatin and lovastatin were added 1 h prior to the addition of the radioactive label. In order to avoid the influence of differences relating to individual donors, one lens from each donor was incubated without drug (control) and the other lens was incubated in the presence of the drug. Statistical analysis showed that the fatty acid synthesis rate was not influenced by the drug. For each lens pair the percentage inhibition of the cholesterol synthesis caused by the drug was calculated. Using various concentrations of the drugs, a dose-response curve was composed for the inhibition of the cholesterol synthesis. The experiments showed that in the human lens organ culture system, lovastatin was 100-fold more potent than pravastatin in inhibiting the cholesterol biosynthesis. To study the in vivo influence of vastatins on the cholesterol content of the developing lens, Wistar rats were weaned at day 21 of age and subsequently the pups were fed a control diet or drug-containing diet (10, 50 or 100 mg lovastatin/kg chow) for a 3-week period. At the end of diet intervention, doses of 50 or 100 mg lovastatin/kg chow had caused a reduction of about 20% of the lenticular cholesterol content compared with controls. No effect on the lens cholesterol content by pravastatin was observed. Both human ex vivo and rat in vivo experiments show that lovastatin much more strongly inhibits the lenticular cholesterol synthesis than does pravastatin.