The influence of the 3-hydroxy-3-methyl-glutaryl
coenzyme A (
HMG-CoA) reductase inhibitors pravastatin and
simvastatin on lens
cholesterol metabolism was investigated in the rat. Short-term organ culture experiments with explanted
lenses from 21-day-old Wistar rats showed that
simvastatin was at least 35 times more effective than
pravastatin in inhibiting
cholesterol synthesis. In vivo the
cholesterol content of the rat lens increased linearly with age. Experiments were designed to answer the question whether
simvastatin and
pravastatin inhibit lens
cholesterol synthesis in vivo, which would result in a reduced
cholesterol accumulation in the lens with age. Young Wistar rats were weaned at an age of 21 days and had ad libitum access to a chow supplemented with 10-100 mg
vastatin kg-1 (
drug consumption: 1.5-15 mg
vastatin kg-1
body weight day-1, respectively) or no additions for 3 weeks. Both drugs induced the
HMG-CoA reductase activity in rat liver microsomes (isolated after 1, 2 and 3 weeks of treatment) to a similar extent. This indicates that the two drugs inhibited hepatic
cholesterol synthesis to a comparable extent. During the whole treatment period no significant differences between control and
drug-treated animals could be observed when the wet weight and
protein content of the
lenses were considered. However, a striking difference between the control group and
pravastatin group (50 mg
drug kg-1 diet) on the one hand and the
simvastatin group (50 mg
drug kg-1 diet) on the other was observed when the
cholesterol content of the
lenses were compared as a function of age.(ABSTRACT TRUNCATED AT 250 WORDS)