Fowler B A, Kardish R M, Woods J S
Lab Invest. 1983 Apr;48(4):471-8.
The effects of indium-chloride (InCl3) on hepatocyte structure and function were studied in male rats injected with doses of 0, 10, 20, or 40 mg of InCl3/kg and killed after 16 hours. Fragmentation and degranulation of the rough endoplasmic reticulum and increased numbers of In- and Fe-containing autophagic lysosomes were the most marked cellular changes observed by electron microscopy. Morphometric analyses of hepatocytes disclosed a maximal 4-fold increase in the volume density of the lysosome compartment and a 2-fold decrease in the volume density of the vacuole compartment. Surface densities of the mitochondrial cristae and rough endoplasmic reticulum were increased by 1.5-fold, whereas the surface densities of the smooth endoplasmic reticulum showed a maximal increase of 7-fold. These structural changes were associated with inhibition of microsomal aniline hydroxylase by as much as 50% and ethoxyresorufin-O-deethylase by as much as 30% but no change in aminopyrine demethylase activity. Microsomal acid phosphatase activity was also decreased to 74% of control, whereas beta-glucuronidase was unchanged. Mild inhibition of mitochondrial respiratory function but no changes in marker enzyme activities were noted. Lysosomal marker enzyme activities were also unaffected, with the exception of acid phosphatase, which was maximally decreased to 55% of control. The data indicate that acute InCl3 injection produces a primary effect on hepatocyte endoplasmic reticulum structure with attendant changes in both heme- and nonheme-dependent biochemical functions. These findings suggest that altered regulation of hepatic microsomal heme metabolism by indium and other metals occurs as part of a general process involving degradative changes in the endoplasmic reticulum structure due to membrane damage with subsequent lysosomal autophagy of nonfunctional components.
研究了氯化铟（InCl₃）对雄性大鼠肝细胞结构和功能的影响。给雄性大鼠注射剂量为0、10、20或40mg/kg的InCl₃，16小时后处死。电子显微镜观察到的最明显的细胞变化是粗面内质网的碎片化和脱颗粒以及含铟和含铁自噬溶酶体数量的增加。肝细胞的形态计量分析显示，溶酶体区室的体积密度最大增加了4倍，液泡区室的体积密度降低了2倍。线粒体嵴和粗面内质网的表面密度增加了1.5倍，而滑面内质网的表面密度最大增加了7倍。这些结构变化与微粒体苯胺羟化酶活性高达50%的抑制以及乙氧基试卤灵-O-脱乙基酶活性高达30%的抑制有关，但氨基比林脱甲基酶活性没有变化。微粒体酸性磷酸酶活性也降至对照的74%，而β-葡萄糖醛酸酶活性未改变。观察到线粒体呼吸功能有轻度抑制，但标记酶活性没有变化。溶酶体标记酶活性也未受影响，但酸性磷酸酶除外，其最大降至对照的55%。数据表明，急性注射InCl₃对肝细胞内质网结构产生主要影响，同时伴有血红素依赖性和非血红素依赖性生化功能的变化。这些发现表明，铟和其他金属对肝微粒体血红素代谢的调节改变是内质网结构因膜损伤而发生降解性变化以及随后非功能性成分溶酶体自噬这一一般过程的一部分。
