[Model systems for study of toxic injury of hepatocytes in vitro].

Ceskoslovenska fysiologie Pub Date : 2006-01-01
Otto Kucera, Halka Lotková, Pavla Kriváková, Tomás Rousar, Zuzana Cervinková
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Abstract

The liver is a common target of toxic effect of a number of xenobiotics, which is in particular a result of its central role in intermediary and energetic metabolism and in biotransformation processes. Ethical, economic, legislative, research and other reasons do not allow testing all of newly-synthesized compounds in in vivo conditions. Hence new methods and approaches for hepatotoxicity testing in vitro have been developing. The most important systems for study of toxicity and metabolic activity in vitro are isolated perfused liver, liver slices, isolated liver cells in suspensions or in primary cultures including co-culture methods and special 3D techniques, various subcellular fractions and stabilised cell lines. These models can be used for cytotoxicity and genotoxicity screening, evaluation of potential hepatoprotective capacity of different compounds, study of toxic injury and characterization of hepatotoxicity mechanisms. Currently there is no an ideal in vitro liver model system for testing of hepatotoxic substances in vitro, nevertheless use of these model systems reduces economic costs and ethic and legislative problems. Model systems in vitro afford opportunity to study in detail mechanisms of hepatotoxicity in comparison with in vivo conditions. Definition of their actual advantages and disadvantages allows choosing a suitable model system for study of particular problem. We cannot imagine current research of liver toxicity without using these model sytems.

[体外肝细胞毒性损伤研究的模型系统]。
肝脏是许多外源药物毒性作用的共同靶点,特别是由于其在中间和能量代谢以及生物转化过程中的核心作用。伦理、经济、立法、研究等原因不允许在体内条件下测试所有新合成的化合物。因此,体外肝毒性检测的新方法和新途径不断发展。体外毒性和代谢活性研究最重要的系统是分离的灌注肝,肝切片,悬浮液或原代培养中的分离肝细胞,包括共培养方法和特殊3D技术,各种亚细胞组分和稳定细胞系。这些模型可用于细胞毒性和遗传毒性筛选,评估不同化合物的潜在肝保护能力,研究毒性损伤和表征肝毒性机制。目前还没有一个理想的体外肝模型系统用于肝毒性物质的体外测试,然而,这些模型系统的使用降低了经济成本和伦理和立法问题。体外模型系统提供了与体内条件比较,详细研究肝毒性机制的机会。明确它们的实际优缺点,以便选择合适的模型系统进行特定问题的研究。如果不使用这些模型系统,我们无法想象目前的肝毒性研究。
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