The effects of mevinolin on serum cholesterol levels of rabbits with endogenous hypercholesterolemia.
Mevinolin, a fungal metabolite isolated from cultures of Aspergillus terreus, is a potent competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis. In the current studies we demonstrate that mevinolin significantly lowers serum cholesterol in rabbits fed a cholesterol free, low-fat semi-synthetic diet. Rabbits maintained on this diet developed endogenous hypercholesterolemia with average cholesterol concentrations of 310 mg/dl over a 66-day period. Treatment with mevinolin for 39 days at a dose of 2 mg/kg per day lowered serum cholesterol levels by an average of 37% (P less than 0.05), while a dose of 6 mg/kg per day resulted in a 48% (P less than 0.05) decrease when compared with the control group. When the administration of mevinolin was discontinued, serum cholesterol levels of the 6 mg/kg per day group increased significantly to a maximum post-treatment value of 319 mg/dl (P less than 0.0001). The results of this study demonstrate that rabbits with endogenous hypercholesterolemia are a useful animal model for the study of cholesterol biosynthesis inhibitors like mevinolin.
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002364:Caseins; D002784:Cholesterol / Q000097:blood*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D006937:Hypercholesterolemia / Q000097:blood*; D008148:Lovastatin; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors; D014908:Triticum
D000924:Anticholesteremic Agents; D002364:Caseins; D009281:Naphthalenes; D002784:Cholesterol; D008148:Lovastatin