In vivo formation of dihydroxylated and glutathione conjugate metabolites derived from thalidomide and 5-Hydroxythalidomide in humanized TK-NOG mice.
In vivo formation of dihydroxylated and glutathione conjugate metabolites derived from thalidomide and 5-Hydroxythalidomide in humanized TK-NOG mice.
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DOI：
10.1021/tx300009j
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发表时间：
2012-02-20
影响因子：
4.1
通讯作者：
Guengerich FP
中科院分区：
文献类型：
--
作者：
Yamazaki H;Suemizu H;Shimizu M;Igaya S;Shibata N;Nakamura M;Chowdhury G;Guengerich FP
在“人源化”肝脏修饰的嵌合小鼠中研究了二羟基沙利度胺和 5-羟基沙利度胺的谷胱甘肽 (GSH) 缀合物的形成：通过引入胸苷激酶制备新型人源化 TK-NOG 小鼠，然后用更昔洛韦诱导，并移植人肝细胞。口服外消旋沙利度胺（100 mg/kg）后，人源化小鼠中 5-羟基和二羟基沙利度胺的血浆浓度高于对照组。给予 5-羟基沙利度胺 (10 mg/kg) 后，检测到较高浓度的二羟基沙利度胺。这些结果表明，人源化小鼠的肝脏介导沙利度胺氧化，在体内产生儿茶酚和/或谷胱甘肽缀合物，并表明沙利度胺发生激活。
The formation of dihydroxythalidomide and glutathione (GSH) conjugate(s) of 5-hydroxythalidomide were investigated in chimeric mice modified with “humanized” liver: novel humanized TK-NOG mice were prepared by introduction of thymidine kinase, followed by induction with ganciclovir, and human liver cells were transplanted. Following oral administration of racemic thalidomide (100 mg/kg), plasma concentrations of 5-hydroxy- and dihydroxythalidomide were higher in humanized mice than in controls. After administration of 5-hydroxythalidomide (10 mg/kg), higher concentrations of dihydroxythalidomide were detected. These results indicate that livers of humanized mice mediate thalidomide oxidation, leading to catechol and/or the GSH conjugate in vivo and suggest that thalidomide activation occurs.
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影响因子：
3.8
作者：
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通讯作者：
Scialli, Anthony R.
影响因子：
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作者：
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作者：
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DOI：
10.1016/j.bbrc.2011.01.042
发表时间：
2011-02-18
影响因子：
3.1
作者：
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通讯作者：
Suemizu H