MECHANISMS OF CARBON-TETRACHLORIDE HEPATOTOXICITY
MECHANISMS OF CARBON-TETRACHLORIDE HEPATOTOXICITY
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DOI：
10.1159/000157141
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发表时间：
1989-03-01
期刊：
影响因子：
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通讯作者：
CLAWSON, GA
中科院分区：
文献类型：
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作者：
CLAWSON, GA
CCl 4长期以来一直作为研究肝毒性的模型化合物。虽然其简单的化学结构具有简单作用机制的吸引力，但数十年的研究揭示了一系列复杂的反应。CCI4给药后的显著早期损伤包括：（1）影响Ca 2+稳态的许多改变，其共同将细胞Ca 2+从内质网和线粒体重新分配到胞质溶胶，和（2）核糖体RNA的低甲基化，其破坏蛋白质合成。体内损伤的发生似乎包括早期的“代谢依赖性”效应（在所研究的水平上，其似乎在很大程度上独立于CCl4浓度）和后期的“代谢独立性”效应（与CCl4浓度平行）。损伤的肝细胞不能对早期损伤做出合成代谢反应可能是CCl 4肝毒性的关键特征。
CCI4 has long served as a model compound for study of hepatotoxicity. While its simple chemical structure held the allure of a simple mechanism of action, decades of study have disclosed a complex series of responses. Significant early damage following CCI4 administration includes:(1) A number of alterations affecting Ca2+ homeostasis, which conspire to redistribute cellular Ca2+ from endoplasmic reticulum and mitochondria to cytosol, and (2) hypomethylation of ribosomal RNA, which disrupts protein synthesis. The genesis of the injury in vivo appears to encompass early'metabolism-dependent'effects (which appear to be largely independent of CCI4 concentration at the levels studied) and later'metabolism-independent'effects, which parallel CCI4 concentration. The inability of injured hepatocytes to respond anabolically to early damage may be a critical feature in CCI4 hepatotoxicity.