The effect of pravastatin on serum cholesterol levels in hypercholesterolemic diabetic rabbits.
Diabetes mellitus is associated with hyperlipidemia and increased risk of atherosclerosis. A diabetic animal model has been developed to study the effect of treatment with pravastatin, a potent HMG CoA reductase inhibitor, on plasma lipoprotein levels. Hypercholesterolemia was induced in alloxan diabetic and control rabbits by feeding a diet containing 25% casein and 10% hydrogenated coconut oil for 8 weeks. Feeding the casein-coconut oil diet to the diabetic group resulted in a 5-fold increase in serum cholesterol levels, which was not statistically different from the nondiabetic group fed this diet. However, in the diabetic group, there was more cholesterol in the VLDL fraction and less in LDL as compared to the nondiabetic group. Serum triacylglycerol levels in the diabetic rabbits were variable and ranged from 58-943 mg/dl. The diabetic and nondiabetic animals were then treated with pravastatin at a dose of 10 mg/kg per day for 21 days. In the nondiabetic group, pravastatin treatment significantly lowered serum and LDL cholesterol concentrations by 28.5% (52.3 mg/dl, P less than 0.05) and 36.2% (40.7 mg/dl, P less than 0.05) respectively, relative to the placebo group. Serum and VLDL triacylglycerol levels in the nondiabetic group were also significantly decreased following pravastatin treatment. In the diabetic group, serum and LDL cholesterol levels were decreased by 37.0% (69.1 mg/dl, P less than 0.05) and 52.7% (32.1 mg/dl, P less than 0.01), respectively, relative to the diabetics given the placebo. Pravastatin treatment did not adversely affect serum glucose levels. Thus, pravastatin treatment was effective in controlling the hypercholesterolemia present in these diabetic animals.
Arbeeny
C M
CM
Department of Metabolic Diseases, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Bergquist
K E
KE
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001053:Apolipoproteins / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D000074263:Coconut Oil; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D010938:Plant Oils / Q000494:pharmacology; D017035:Pravastatin; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D009281:Naphthalenes; D010938:Plant Oils; D014280:Triglycerides; C030104:lipoprotein cholesterol; D002784:Cholesterol; D017035:Pravastatin; D000074263:Coconut Oil