Kucera Otto, Lotková Halka, Kand'ár Roman, Hézová Renata, Muzáková Vladimíra, Cervinková Zuzana
Department of Physiology, Charles University in Prague, Faculty of Medicine, Hradec Králové, Czech Republic.
Acta Medica (Hradec Kralove). 2006;49(1):59-65.
D-galactosamine (GalN) is a highly selective hepatotoxin that causes liver damage similar to human viral hepatitis via depletion of uridine nucleotides, which subsequently diminishes synthesis of RNA and proteins. Model of galactosamine hepatotoxicity is frequently used in animal experiments in vitro. The purpose of our study was to establish the model of GalN-induced hepatocyte injury in in vitro conditions using primocultures of rat hepatocytes as an important pre-requisite for further experiments in which we would like to study potential hepatoprotective effect of various substances. Rate of hepatocyte injury was evaluated by morphological changes, changes in cell viability, albumin production, mitochondrial membrane potential, activity of mitochondrial dehydrogenases and glutathione content. Marked dose dependent hepatocyte injury was found after 24-hour incubation with GalN. Based on the results we suggest as an optimal model for short-term toxicity test exposure to GalN for 24 hours in dose of 40 mM.
D-半乳糖胺(GalN)是一种高度选择性的肝毒素,它通过消耗尿苷核苷酸导致类似于人类病毒性肝炎的肝损伤,进而减少RNA和蛋白质的合成。半乳糖胺肝毒性模型常用于体外动物实验。我们研究的目的是利用大鼠原代肝细胞建立体外条件下半乳糖胺诱导的肝细胞损伤模型,这是我们进一步研究各种物质潜在肝保护作用的重要前提实验。通过形态学变化、细胞活力变化、白蛋白产生、线粒体膜电位、线粒体脱氢酶活性和谷胱甘肽含量来评估肝细胞损伤率。与GalN孵育24小时后发现明显的剂量依赖性肝细胞损伤。基于这些结果,我们建议将40 mM剂量的GalN暴露24小时作为短期毒性试验的最佳模型。