In vivo formation of a glutathione conjugate derived from thalidomide in humanized uPA-NOG mice.
In vivo formation of a glutathione conjugate derived from thalidomide in humanized uPA-NOG mice.
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DOI：
10.1021/tx200005g
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发表时间：
2011-03-21
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;Igaya S;Shimizu M;Shibata N;Nakamura M;Chowdhury G;Guengerich FP
致畸剂沙利度胺的代谢与其毒理学作用相关。我们证明了（R）-5-羟基沙利度胺的谷胱甘肽（GSH）缀合物在具有人源化肝脏的嵌合NOD-scid IL 2 Rgnull小鼠（uPA-NOG小鼠）中的体内形成。口服外消旋沙利度胺（270 mg/kg）后，人源化小鼠中5-羟基沙利度胺的血浆浓度显著高于对照小鼠。在血浆中检测到5-羟基沙利度胺的GSH结合物。这些结果表明，人源化小鼠的肝脏介导沙利度胺5-羟基化和进一步氧化，导致体内以及体外GSH缀合物，并表明沙利度胺活化发生。
Metabolism of the teratogen thalidomide is proposed to be relevant to its toxicological action. We demonstrated formation of the glutathione (GSH) conjugate of (R)-5-hydroxythalidomide in vivo in chimeric NOD-scid IL2Rgnull mice with humanized liver (uPA-NOG mice). After an oral administration of racemic thalidomide (270 mg/kg), plasma concentrations of 5-hydroxythalidomide were significantly higher in humanized mice than in control mice. The GSH conjugate of 5-hydroxythalidomide was detected in the plasma. These results indicate that livers of humanized mice mediate thalidomide 5-hydroxylation and further oxidation leading to the GSH conjugate in vivo as well as in vitro and suggest that thalidomide activation occurs.
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影响因子：
3.6
作者：
Ando, L;Price, DK;Figg, WD
通讯作者：
Figg, WD
影响因子：
4.1
作者：
Chowdhury, Goutam;Murayama, Norie;Yamazaki, Hiroshi
通讯作者：
Yamazaki, Hiroshi
影响因子：
3.3
作者：
Eriksson, T;Björkman, S;Höglund, P
通讯作者：
Höglund, P
DOI：
10.1002/tera.1420380303
发表时间：
1988-09-01
期刊：
TERATOLOGY
影响因子：
--
作者：
LENZ, W
通讯作者：
LENZ, W
影响因子：
56.9
作者：
Ito, Takumi;Ando, Hideki;Handa, Hiroshi
通讯作者：
Handa, Hiroshi