Development of a microscale cell culture analog to probe naphthalene toxicity
Development of a microscale cell culture analog to probe naphthalene toxicity
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DOI：
10.1021/bp0341996
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发表时间：
2004-01-01
影响因子：
2.9
通讯作者：
Shuler, ML
中科院分区：
文献类型：
--
作者：
Viravaidya, K;Sin, A;Shuler, ML
由于生物体的复杂性，很难预测人类对药物或化学品的反应。我们描述了一种体外模型，可以现实和廉价地研究吸附，分布，代谢，消除和潜在的毒性（ADMET）的化学品。微尺度细胞培养模拟物（muCCA）是基于生理学的药代动力学（PBPK）模型的物理复制品。这种微加工装置由模拟循环系统的通道的流体网络和含有代表动物“器官”系统的关键功能的培养的哺乳动物细胞的腔室组成。本文描述了一种双细胞系统、四腔室muCCA（“肺”-“肝”-“其他组织”-“脂肪”）装置在使用萘作为模型毒物的概念验证研究中的应用。萘被转化成反应性代谢物（即，1，2-萘醌和1，2-萘醌），然后循环到“肺”消耗肺细胞中的谷胱甘肽（GSH）。这种微制造的体外装置是用于测试化学品和药物的毒性和功效的潜在人类替代物。
Prediction of human response to drugs or chemicals is difficult as a result of the complexity of living organisms. We describe an in vitro model that can realistically and inexpensively study the adsorption, distribution, metabolism, elimination, and potential toxicity (ADMET) of chemicals. A microscale cell culture analog (muCCA) is a physical replica of the physiologically based pharmacokinetics (PBPK) model. Such a microfabricated device consists of a fluidic network of channels to mimic the circulatory system and chambers containing cultured mammalian cells representing key functions of animal "organ" systems. This paper describes the application of a two-cell system, four-chamber muCCA ("lung"-"liver"-"other tissue"-"fat") device for proof-of-concept study using naphthalene as a model toxicant. Naphthalene is converted into reactive metabolites (i.e., 1,2-naphthalenediol and 1,2-naphthoquinone) in the "liver" compartment, which then circulate to the "lung" depleting glutathione (GSH) in lung cells. Such microfabricated in vitro devices are potential human surrogates for testing chemicals and pharmaceutics for toxicity and efficacy.