Carpenter H M, Hedstrom O R, Siddens L K, Duimstra J R, Cai Z W, Fisher K A, Curtis L R
Oak Creek Laboratory of Biology, Oregon State University, Corvallis 97331, USA.
Fundam Appl Toxicol. 1996 Nov;34(1):157-64. doi: 10.1006/faat.1996.0186.
Pretreatment of mice with chlordecone (CD) reduced hepatic accumulation of a subsequent dose of [14C]CD without significantly changing [14C]CD biotransformation. To determine if CD-induced changes in hepatic [14C]CD accumulation were coincident with altered cell composition, we examined the effects of CD on hepatic protein and lipid content, on fatty acid profiles of liver and kidney, and on the ultrastructure of hepatocytes. SDS-polyacrylamide gel electrophoresis detected an apparent CD dose-related increase in a microsomal protein with a molecular weight of about 23 kDa. Total liver or kidney lipid contents were not altered by CD but relative amounts of several hepatic fatty acids were changed. CD caused marked hepatic mitochondrial swelling, increased amounts of endoplasmic reticulum, apparently increased numbers of peroxisome-like structures, and decreased numbers of lipid droplets in cytoplasm of hepatocytes. Numbers of lipid droplets were not decreased in perisinusoidal fat storage cells. In addition, the numbers of cytoplasmic lipoprotein vesicles were apparently increased in some hepatocytes. Overall these changes indicated an increased hepatocyte secretory activity and suggested that CD changed hepatocellular lipid transport, storage, and metabolism pathways.
用开蓬（CD）对小鼠进行预处理，可减少后续剂量的[14C]CD在肝脏中的蓄积，而不会显著改变[14C]CD的生物转化。为了确定CD诱导的肝脏[14C]CD蓄积变化是否与细胞组成改变同时发生，我们研究了CD对肝脏蛋白质和脂质含量、肝脏和肾脏脂肪酸谱以及肝细胞超微结构的影响。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳检测到一种分子量约为23 kDa的微粒体蛋白出现明显的与CD剂量相关的增加。CD未改变肝脏或肾脏的总脂质含量，但改变了几种肝脏脂肪酸的相对含量。CD导致肝脏线粒体明显肿胀、内质网数量增加、过氧化物酶体样结构数量明显增多，且肝细胞胞质内脂滴数量减少。肝窦周脂肪储存细胞中的脂滴数量未减少。此外，一些肝细胞中胞质脂蛋白囊泡的数量明显增加。总体而言，这些变化表明肝细胞分泌活性增强，并提示CD改变了肝细胞脂质转运、储存和代谢途径。
