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首页> 外文期刊>Applied in vitro toxicology. >A Novel In Vitro Liver Cell Culture Flow System Allowing Long-Term Metabolism and Hepatotoxicity Studies
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A Novel In Vitro Liver Cell Culture Flow System Allowing Long-Term Metabolism and Hepatotoxicity Studies

机译：一种新的体外肝细胞培养流程系统允许长期代谢和肝毒性研究

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Introduction: Hepatotoxicity is a concern when developing new pharmaceutical compounds. Animal models do not accurately predict toxicity in humans due to species differences, for example, in compound metabolism. In this study, we present an alternative in vitro model based on the culture of primary human hepatocytes (PHH) in the Quasi Vivo~(?) QV900 Flow System. Materials and Methods: PHH were kept in sandwich culture in static and in perfused conditions. During 3 weeks of culture, viability and albumin content were quantified. Basal and induced cytochrome P450 (CYP) enzyme activity were assessed by luminescence assay and analysis of metabolite formation. Results: Good cell viability and sustained albumin production were observed in perfused culture. In comparison to nonperfused cultures, the basal activity of the drug metabolism enzymes CYP3A4, CYP1A2, and CYP2B6 was increased. Induced CYP3A4 activity was comparable between perfused and nonperfused cultures. Furthermore, the QV900 System allowed fewer medium changes as typically required in static cultures. This enables buildup of potential toxic metabolites that would otherwise not be detected when media are refreshed daily. Discussion: PHH can be cultured in the QV900 Flow System for 3 weeks with only two medium changes per week. Improved basal CYP activity was observed in comparison to static culture. Conclusion: We present a liver cell culture flow system that improves longer-term stability of drug metabolism enzymes in PHH and is therefore a more human-relevant in vitro model for repeat dosing of hepatotoxicants.
机译：作品简介:肝毒性是一个考虑开发新药物。模型不准确预测毒性人类由于物种差异,例如,在化合物代谢。另一种基于体外模型主要的文化人类肝细胞(收购PHH)准的~ (?)方法:在收购PHH三明治文化在灌注条件下静态和。文化、生存能力和白蛋白含量量化。(CYP)酶活性进行了评估发光代谢物的测定和分析形成。持续的白蛋白生产观察包括文化。文化中,药物的基础活动CYP3A4代谢酶、CYP1A2和CYP2B6增加了。灌注和nonperfused之间的文化。此外,QV900系统允许更少媒介的变化通常需要在静态的文化。代谢物,否则不能被检测到当媒体每天刷新。可以培养QV900流系统3每周周只有两个介质的变化。改善基底CYP活动中观察到比较静态文化。肝细胞培养流程系统提高药物代谢的长期稳定酶在收购PHH因此更重复剂量human-relevant体外模型of hepatotoxicants .

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