Reconstituted epidermis: a novel model for the study of drug metabolism in human epidermis.
Reconstituted epidermis: a novel model for the study of drug metabolism in human epidermis.
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DOI：
10.1111/1523-1747.ep12874606
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发表时间：
1990-06
期刊：
影响因子：
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通讯作者：
M. Pham;J. Magdalou;G. Siest;M. Lenoir;B. Bernard;J. Jamoulle;B. Shroot
中科院分区：
文献类型：
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作者：
M. Pham;J. Magdalou;G. Siest;M. Lenoir;B. Bernard;J. Jamoulle;B. Shroot
测定了人毛囊外根鞘细胞重建表皮的代谢能力。研究发现，该表皮具有参与药物生物转化的第一相（氧化）和第二相（结合）反应的酶。模型底物的使用允许对几种同工酶进行表征。匀浆部分含有参与 7-乙氧基-、7-戊氧基-和 7-苯氧基异卤灵 O-脱烷基化的膜结合混合功能氧化酶（细胞色素 P-450 依赖性）、NADPH 细胞色素 c (P-450) 还原酶、睾酮 5 α-还原酶和 UDP-葡萄糖醛酸基转移酶，它们与 1-萘酚和胆红素。检测到作用于雌酮和 4-甲基伞形酮硫酸盐的谷胱甘肽 S-转移酶、类固醇硫酸酯酶和芳基硫酸酯酶各有一种同工型。此外，还可以测量两种不同形式的环氧化物水解酶的活性，它们水合顺式和反式二苯乙烯氧化物。重建表皮中这些药物代谢酶的存在表明它有潜力作为体外研究表皮药物代谢的模型。
The metabolic capacity of reconstituted epidermis from the outer root sheath cells of human hair follicles was determined. It was found that this epidermis possesses enzymes involved in both phase I (oxidation) and phase II (conjugation) reactions for drug biotransformation. The use of model substrates allowed the characterization of several isoenzymes. The homogenate fraction contained membrane-bound mixed-function oxydases (cytochrome P-450 dependent) involved in the O-dealkylation of 7-ethoxy-, 7-pentoxy-, and 7-benzoxyresorufin, NADPH cytochrome c (P-450) reductase, testosterone 5 alpha-reductase, and UDP-glucuronosyltransferases, which conjugate 1-naphthol and bilirubin. One isoform of each glutathione S-transferase, steroid-, and arylsulfatases, acting on estrone- and 4-methylumbelliferone sulfates, was detected. Additionally, the activity of two distinct forms of epoxide hydrolases, which hydrate cis- and trans-stilbene oxides, could be measured. The presence of these drug metabolizing enzymes in the reconstituted epidermis indicates that it has a potential to serve as a model to study epidermal drug metabolism in vitro.