Development of the hepatic toxicity evaluation test using a mini-bioartificial liver and ^<13>C stability isotope compounds

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The xinobiotic evaluation method used by human cells is a technique to fill metabolic differences between Homo sapiens and experimental animals. However, conventional single-layered culture method cannot reproduce the functions of cell in the body. We can use the bioartificial organs which we made by three-dimensional high density culture method as a substitute organ of human tissue and organs. In the present study, we performed development of the metabolic and toxic test using ^<13>C stability isotope compounds for sensitive metabolic evaluation in a substitute organ.Three-dimensional culture in a bioreactor is a large-scaled culture compared to single-layered culture. Therefore it is difficult to operate a lot of reactors. On this account a system to carefully judge the operation situation of one reactor is necessary. At first we made a mixed gas feeder to maintain simply three-dimensional culture system, without a CO_2 incubator and a large-scaled controller, supplied oxygen of cult … More ure system. I also developed the metabolism discharge ^<13>CO_2 assay method using a ^<13>C stability isotope labeled compound to perform toxic evaluation and a certain specific metabolism evaluation on culture course. The advantages of this method are ; 1)We can evaluate a specific metabolism by using a specific labeled compound, 2)We can easily get samples as exhaust gas from a reservoir, and do not need to open a reactor, and 3) We can easily measure ^<13>CO_2 for only 2'30" by a infrared spectrophotometer.As a result of this study, we developed the metabolic and toxic evaluation system for performing metabolic simulation in the body using bioartificial organs and ^<13>C stability isotope labeled compounds. Objective evaluation will apply metabolism modeling and computer simulation. Before animal and clinical examinations, the substitute analysis using bioartificial organs and a stability isotope labeled compounds will become useful for evaluation of the toxicity/metabolism of quality of drugs and foods in future. Less