Effect of lovastatin on hypercholesterolemia in chronic renal failure.
Using a mouse model of chronic renal failure (CRF), the possibility of using lovastatin to treat hypercholesterolemia associated with CRF was examined. Renal failure was induced in 5 week-old, C57BL/6J mice by electrocoagulation of the right kidney surface followed by left nephrectomy 2 weeks later. Five weeks post-nephrectomy, BUN and serum total cholesterol levels were assessed and lovastatin treatment commenced. Upon sacrifice 4 weeks later, BUN, serum total cholesterol levels and hepatic HMG-CoA reductase activity were measured. Results showed that CRF induced significant increases in serum total cholesterol levels and enzyme activity. Treatment with lovastatin led to a dose-dependent reduction in serum total cholesterol levels without affecting the enzyme activity. These results suggest that the hyper-cholesterolemia in CRF is partly due to an increase in de novo cholesterol synthesis in the liver and that the lipid-lowering effect of lovastatin is mediated by an action other than the direct reduction of hepatic HMG-CoA reductase activity.
Subang
M C
MC
Department of Physiology, McGill University, Montreal, Canada.
Stewart-Phillips
J L
JL
Gagnon
R F
RF
D000818:Animals; D001806:Blood Urea Nitrogen; D002784:Cholesterol / Q000097:blood; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications*; D008148:Lovastatin / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL
D002784:Cholesterol; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases