CNRS-UMR 6600, Laboratoire de biomécanique et de bio ingénierie, Université de Technologie de Compiègne, BP 20529, 60205 Compiègne Cedex, France.
Toxicol In Vitro. 2011 Aug;25(5):1123-31. doi: 10.1016/j.tiv.2011.03.017. Epub 2011 Mar 30.
In this study we present a method for investigating the effect of acrolein, a nephrotoxic and urotoxic metabolite of the anticancerous prodrugs ifosfamide and cyclophosphamide, in a blood-renal barrier biochip. The real time monitoring of mass transfers of caffeine, vitamin B12 and albumin in the biochip was performed thanks to an in vitro dialysis method. The diffusion coefficients of the solutes and their dialysance from the apical to the basolateral compartments were found to be molecular weight and cell-membrane dependent, thus demonstrating the cell-barrier functionality. The toxicity induced by the acrolein led to modifications to mass transfer properties which appeared to be acrolein dose, time and solute molecular weight dependent. Solute mass transfer across the cell layer increased with acrolein concentrations. The sensitivity of this analysis method contributes to identify the mass transfer properties and to monitor the modification to the renal parameter when submitted to toxic cell compounds. The results provide the foundation for exploring kidney behavior in response to drugs thanks to a blood-tissue barrier model using a technique based on in vitro dialysis and real time analysis.
在这项研究中,我们提出了一种方法来研究丙烯醛的影响,丙烯醛是抗癌前药异环磷酰胺和环磷酰胺的肾毒性和尿毒性代谢物,在血肾屏障生物芯片中。通过体外透析法实时监测生物芯片中咖啡因、维生素 B12 和白蛋白的质量转移。发现溶质的扩散系数及其从顶侧向基底侧隔室的透析率与分子量和细胞膜有关,从而证明了细胞屏障的功能。丙烯醛引起的毒性导致质量转移特性发生变化,这些变化似乎与丙烯醛剂量、时间和溶质分子量有关。溶质穿过细胞层的质量转移随着丙烯醛浓度的增加而增加。这种分析方法的灵敏度有助于确定质量转移特性,并在受到有毒细胞化合物时监测对肾脏参数的修改。该结果为探索药物对肾脏的作用提供了基础,这要归功于一种基于体外透析和实时分析的血组织屏障模型。