Inhibitory Effects of Pravastatin, a Competitive Inhibitor of Hydroxymethylglutaryl Coenzyme A Reductase, on Cholesterol Gallstone Formation in Prairie Dogs

Abstract

The effects of pravastatin on cholesterol gallstone formation were determined in prairie dogs. We fed 10 prairie dogs 1 % cholesterol with or without 0.05% (w/w) pravastatin (n = 5, each) for 4 weeks. In addition, another 5 prairie dogs were fed a standard rodent chow as a control. Only the animals fed 1 % cholesterol without pravastatin treatment formed cholesterol gallstones. Gallbladder bile from cholesterol-fed animals contained cholesterol monohydrate crystals, whereas those treated with pravastatin contained no crystal. Furthermore, marked increases in tissue cholesterol levels (serum, liver and bile), and in biliary mucous glycoprotein levels were evident in cholesterol-fed animals, whereas pravastatin treatment normalized these levels. These findings raise the possibility that such inhibitors might have a future role to play in the prevention of cholesterol gallstone formation and/or recurrence.