Anthony L E, Schmucker D L, Mooney J S, Jones A L
J Lipid Res. 1978 Feb;19(2):154-65.
The effects of clofibrate on the fine structure and drug-metabolizing capacity of livers of normolipidemic young adult virgin (YA) and hypercholesterolemic retired breeder (RB) male rats were measured by morphometric and biochemical procedures. The oral administration of clofibrate for 7 days significantly increased liver weight and reduced the cholesterol concentrations in the serum and liver tissue in both groups of animals. The hepatic triglyceride (TG) concentration and the volume of cytoplasmic lipid droplets, presumably TG, as well as the serum TG concentration, increased only in the drug-treated RB rats. Clofibrate treatment resulted in significant increases in the volumes of the hepatocytes and their constituent mitochondria and microbodies and caused a proliferation of the smooth-surfaced endoplasmic reticulum. Although the magnitude of the hypocholesterolemic response was considerably greater in the RB animals, the morphological changes were much more marked in the YA group. However, the surface area of the rough-surfaced endoplasmic reticulum was reduced in the livers of the drug-treated RB rats. NADPH cytochrome c reductase specific activity was significantly increased in both the RB and YA animals, but the concentration of cytochrome P-450 (per mg microsomal protein) increased only in the YA rats. Neither the cytochrome b5 concentration nor the rate of ethylmorphine N-demethylation was significantly affected by clofibrate administration. The results suggest that there is no positive correlation between the hypocholesterolemic response to clofibrate and the degree of subcellular changes in the hepatocytes and that this hypolipidemic drug elicits a minimal effect on the concentrations of the components of the hepatic microsomal drug-metabolizing system.
通过形态计量学和生化方法，测定了氯贝丁酯对正常血脂的年轻成年未交配雄性大鼠（YA）和高胆固醇血症的老年繁殖雄鼠（RB）肝脏的精细结构和药物代谢能力的影响。对两组动物口服氯贝丁酯7天，均显著增加了肝脏重量，并降低了血清和肝组织中的胆固醇浓度。肝甘油三酯（TG）浓度、细胞质脂滴（可能是TG）的体积以及血清TG浓度仅在药物处理的RB大鼠中增加。氯贝丁酯治疗导致肝细胞及其组成的线粒体和微体体积显著增加，并引起滑面内质网增生。尽管RB动物的降胆固醇反应幅度大得多，但形态学变化在YA组更为明显。然而，药物处理的RB大鼠肝脏中粗面内质网的表面积减少。NADPH细胞色素c还原酶的比活性在RB和YA动物中均显著增加，但细胞色素P-450（每毫克微粒体蛋白）的浓度仅在YA大鼠中增加。氯贝丁酯给药对细胞色素b5浓度和N-脱甲基乙基吗啡的速率均无显著影响。结果表明，对氯贝丁酯的降胆固醇反应与肝细胞亚细胞变化程度之间无正相关，且这种降血脂药物对肝微粒体药物代谢系统各成分的浓度影响极小。
