1,1-Dichloroethylene hepatotoxicity. Time course of GSH changes and biochemical aberrations.
1,1-Dichloroethylene hepatotoxicity. Time course of GSH changes and biochemical aberrations.
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发表时间：
1980-11
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通讯作者：
Edward S. Reynolds;M. T. Moslen;P. Boor;Rudolph J. Jaeger
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作者：
Edward S. Reynolds;M. T. Moslen;P. Boor;Rudolph J. Jaeger
将禁食大鼠暴露于200 ppm 1，1-二氯乙烯（1，1-DCE）1-4小时导致肝脏Na、K、Ca和GSH水平显著异常，这些异常发生在肝脏灾难性组织学改变之前和/或伴随肝脏灾难性组织学改变。Na水平在第一个小时内开始上升，并且在形态学上明显的损伤之前。Ca水平显着增加，K水平下降之间的第二和第四小时的曝光，并伴随着灾难性的形态学改变。GSH水平迅速耗尽，但在暴露于1，1-DCE结束前开始恢复。肝内质网的混合功能氧化酶系统的组件的功能没有受到明显的影响，在早期的过程中的1，1-DCE曝光，但损伤后变得巨大，细胞色素P-450和氧化N-脱甲基酶失活。因此，对内质网混合功能氧化酶系统功能组分的影响似乎不是1，1-DCE细胞毒性的主要事件。与此相反，有线粒体K的进行性下降和线粒体Na，Zn和Mg的显着不平衡之前大量涌入的Ca到细胞中，表明线粒体参与早期的损伤性分子事件的演变引起的这种强大的肝毒素。
Exposure of fasted rats to 200 ppm 1,1-dichloroethylene (1,1-DCE) for 1-4 hours resulted in striking aberrations in hepatic Na, K, Ca, and GSH levels which preceded and/or accompanied catastrophic histologic alterations of the liver. Na levels began to rise during the first hour, and preceded the morphologically apparent injury. Ca levels increased markedly and K levels declined between the second and fourth hour of exposure, and accompanied the catastrophic morphologic alterations. GSH levels were rapidly depleted but began to recover before the end of the exposure to 1,1-DCE. Functions of components of the mixed-function oxidase system of the liver endoplasmic reticulum were not appreciably affected early in the course of 1,1-DCE exposure; but after injury became massive, cytochrome P-450 and oxidative N-demethylase were deactivated. Thus effects on the functional components of the endoplasmic reticulum mixed-function oxidase system do not appear to be primary events in 1,1-DCE cytotoxicity. In contrast, there were progressive declines in mitochondrial K and marked imbalances in mitochondrial Na, Zn, and Mg preceding the massive influx of Ca into the cell, indicating that mitochondria are involved early in he evolution of injurious molecular events elicited by this potent hepatotoxin.