Alteration of hepatocellular structure and function by thallium chloride: ultrastructural, morphometric, and biochemical studies.
Alteration of hepatocellular structure and function by thallium chloride: ultrastructural, morphometric, and biochemical studies.
复制标题
氯化铊改变肝细胞结构和功能：超微结构、形态测量和生化研究。
DOI：
10.1016/0041-008x(86)90299-1
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发表时间：
1986
影响因子：
3.8
通讯作者：
B. Fowler
中科院分区：
文献类型：
--
作者：
J. S. Woods;B. Fowler
研究了氯化铊（TlCl3•4H2O）对雄性大鼠肝细胞结构和功能的影响，其剂量分别为0、50、100和200 mg/kg。铊处理大鼠肝细胞的超微结构检查显示内质网核糖体的剂量相关损失和粗内质网段的增殖。线粒体普遍肿胀，电子致密自噬溶酶体数量增加。对铊处理大鼠肝细胞的形态计量学分析显示，溶酶体腔室的体积密度增加了3倍，线粒体的体积密度增加了1.3倍。线粒体和内质网膜的表面密度测量显示，线粒体内外膜以及粗内质网的表面密度均随剂量增加而增加。这些结构变化与线粒体膜相关酶单胺氧化酶和铁螯合酶的比活性显著增加有关，分别达到对照值的145和144%，氨基乙酰丙酸合成酶的活性下降42%。同样，铊处理大鼠内质网的结构改变与微粒体酶NADPH、细胞色素c （P-450）还原酶、苯胺羟化酶和氨基芘去甲基化酶的同时损伤有关，其活性分别高达未处理对照组的49%、43%和77%。相比之下，非膜结合酶苹果酸脱氢酶、ALA脱氢酶和尿卟啉原I合成酶在任何剂量的铊处理后都没有改变。这些结果表明，铊诱导的肝脏生化过程的改变可能是由亚细胞细胞器的膜完整性的物理破坏引起的，这些过程在功能上与之相关。这些发现与先前的研究结果一致，表明金属诱导的亚细胞细胞器膜结构损伤与体内相关生物学功能障碍之间存在正相关的定量关系。
The effects of thallium chloride (TlCl3•4H2O) on hepatocyte structure and function were studied in male rats at 16 hr following treatment by ip injection with doses of 0, 50, 100, and 200 mg/kg. Ultrastructural examination of hepatocytes from thallium-treated rats showed a dose-related loss of ribosomes from the endoplasmic reticulum and proliferation of the rough endoplasmic reticulum segment. Generalized mitochondrial swelling and increased numbers of electron-dense autophagic lysosomes were also observed. Morphometric analysis of hepatocytes from thallium-treated rats disclosed a 3-fold increase in the volume density of the lysosomal compartment and a 1.3-fold increase in the volume density of mitochondria. Surface density measurements of mitochondrial and endoplasmic reticulum membranes showed dose-related increases in the surface density of both inner and outer mitochondrial membranes as well as of the rough endoplasmic reticulum. These structural changes were associated with pronounced increases in the specific activities of the mitochondrial membrane-associated enzymes monoamine oxidase and ferrochelatase to 145 and 144% of control values, respectively, and a 42% decrease in the activity of aminolevulinic acid (ALA) synthetase. Similarly, structural alteration of the endoplasmic reticulum in thallium-treated rats was associated with concomitant impairment of the microsomal enzymes NADPH cytochrome c (P-450) reductase, aniline hydroxylase, and aminopyrene demethylase to a maximum of 49, 43, and 77% of activities seen in untreated controls, respectively. In contrast, the non-membrane-bound enzymes malate dehydrogenase, ALA dehydratase, and uroporphyrinogen I synthetase were unaltered in vivo following thallium treatment at any doses. These results indicate that thallium-induced alteration of hepatic biochemical processes may arise from physical disruption of the membranal integrity of subcellular organelles with which those processes are functionally associated. These findings are consistent with those from previous studies in demonstrating a positive quantitative correlation between metal-induced subcellular organelle membrane structural injury and impairment of associated biological functions in vivo.
DOI：
--
发表时间：
1982-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
S. D. Black;Minor;Coon
通讯作者：
S. D. Black;Minor;Coon
影响因子：
3.8
作者：
FOWLER, BA;KIMMEL, CA;GRANT, LD
通讯作者：
GRANT, LD