Kinetic analysis on the skin disposition of cytotoxicity as an index of skin irritation produced by cetylpyridinium chloride:: Comparison of in vitro data using a three-dimensional cultured human skin model with in vivo results in hairless mice
Kinetic analysis on the skin disposition of cytotoxicity as an index of skin irritation produced by cetylpyridinium chloride:: Comparison of in vitro data using a three-dimensional cultured human skin model with in vivo results in hairless mice
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DOI：
10.1007/s11095-006-9141-z
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发表时间：
2006-02-01
影响因子：
3.7
通讯作者：
Sugibayashi, K
中科院分区：
文献类型：
--
作者：
Kano, S;Sugibayashi, K
本研究的目的是利用三维培养的人体皮肤模型对作为皮肤刺激指标的体外细胞毒性进行动力学和动态分析，并将体外测定数据与活体动物的数据进行比较。选择阳离子表面活性剂氯化十六烷基吡啶(CPC)作为模型刺激物。活体皮肤当量高（LSE-高）和无毛小鼠分别用于体外和体内测试。通过噻唑蓝 (MTT) 量热转换测定法评估体外和体内测试的皮肤刺激性皮肤动力学，而使用 HPLC 评估 CPC 在 LSE 高小鼠和小鼠皮肤中的皮肤动力学。在 LSE 高小鼠和无毛小鼠中，将 CPC 应用于完整皮肤后，皮肤中细胞活力的时间过程与角质层剥离的皮肤明显不同。在完整皮肤中观察到以具有拐点时间点的两个一级速率为特征的双相行为，而在剥离皮肤中应用 CPC 后，细胞活力立即单指数下降。皮肤细胞活力和皮肤动力学的时间进程与CPC的皮肤动力学密切相关。本研究表明，体外细胞毒性特征与体内细胞毒性测试相似，并且皮肤动力学与CPC的皮肤动力学相关。
The aim of this study was to kinetically and dynamically analyze in vitro cytotoxicity as an index of skin irritation by use of a three-dimensional cultured human skin model and to compare the in vitro assay data with data from living animals.A cationic surfactant, cetylpyridinium chloride (CPC), was selected as a model irritant. Living skin equivalent-high (LSE-high) and hairless mice were used for the in vitro and in vivo tests, respectively. Skin irritation dermatodynamics was evaluated by calorimetric thiazoyl blue (MTT) conversion assay both for in vitro and in vivo tests, whereas dermatokinetics of CPC in LSE-high and mouse skin were evaluated using HPLC.The time course of cell viability in the skin after application of CPC to intact skin was distinctly different from that of stratum-corneum-stripped skin in both LSE-high and hairless mice. Biphasic behavior characterized by two first-order rates with an inflection time point was observed in intact skin, whereas cell viability monoexponentially decreased immediately after CPC application in stripped skin. The time courses of cell viability in the skin and dermatodynamics were closely related to that of dermatokinetics of CPC.The present study demonstrates that the in vitro cytotoxic profile was similar to the in vivo cytotoxicity test and that dermatodynamics was related to dermatokinetics of CPC.