Cholesterol content of the rat lens is lowered by administration of simvastatin, but not by pravastatin.
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)
De Vries
A C
AC
TNO Institute of Ageing and Vascular Research (IVVO-TNO), Gaubius Laboratory, Leiden, The Netherlands.
Vermeer
M A
MA
Bredman
J J
JJ
Bär
P R
PR
Cohen
L H
LH
D000375:Aging / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002784:Cholesterol / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D009924:Organ Culture Techniques; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin; D013997:Time Factors
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin