Abstract
The effects of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, were investigated in cholesterol-fed rabbits.
Experimental rabbits were divided into 4 groups. Group A received simvastatin (10mg/kg/day) orally for 5 weeks and group B received the same dose for 10 weeks (simvastatin groups). The control groups C and D received a placebo for 5 and 10 weeks, respectively. The levels of serum total cholesterol (T-C), triglyceride (T-G), β-lipoprotein and high density lipoprotein cholesterol (HDL-C) were measured every week. At the end of the experimental period the aortas were removed, opened longitudinally and stained with Sudan III.
Both placebo groups showed a significant increase in T-C, T-G and β-lipoprotein concentrations, but the simvastatin groups did not show such an increase. There were no significant differences in HDL-C levels between the simvastatin and placebo groups. Integrated values of T-C (Integrated T-C, mg·day/d/) were 8, 318.1 in group A, 10, 152.1 in group B, 28, 754.6 in group C and 73, 430.0 in group D. Aortic surface involvement (S·I, %) was 0.5 in group A, 0.3 in group B, 7.5 in group C and 16.6 in group D. S·I was related closely with the integrated T-C (r=0.899).
These results demonstrate the suppressive effects of simvastatin on atherogenesis by reducing hypercholesterolemia.
Total lipids in feces excreted during a 24-hour period were measured. Fecal lipids had increased two-fold in the simvastatin group (5mg/kg/day). It was suggested that simvastatin may accelerate the lipid excretion into the intestine.
