Effects of single administration of pravastatin sodium on hepatic cholesterol metabolism in rats.
Pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was administered to rats at 500 mg/kg, and the changes in several parameters concerning the metabolism of cholesterol in the liver were determined over 12 h. HMG-CoA reductase activity began to be induced 6 h after pravastatin dosage and continued to increase for an additional 6 h. A significant reduction of serum and liver microsomal cholesterol was observed only at 9 h. At this time point, the protein mass and activity of cholesterol 7 alpha-hydroxylase were significantly decreased by 31% and 34%, respectively. Hepatic low density lipoprotein (LDL) receptor expression was not affected by pravastatin throughout the experimental period. These results suggest that, in rats, the compensatory mechanism to restore the cholesterol balance after depletion of liver cholesterol produced by a single administration of pravastatin might primarily depend on the induction of HMG-CoA reductase and might be facilitated by a reduction in cholesterol 7 alpha-hydroxylase, without the induction of hepatic LDL receptor.
Fujioka
T
T
Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.fujiok@shina.sankyo.co.jp
Tsujita
Y
Y
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000378:metabolism
D000924:Anticholesteremic Agents; D011973:Receptors, LDL; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D002790:Cholesterol 7-alpha-Hydroxylase; D017035:Pravastatin