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.