In Vivo Formation of a Glutathione Conjugate Derived from Thalidomide in Humanized uPA-NOG Mice

详细信息    查看全文

• 作者：Hiroshi Yamazaki ; Hiroshi Suemizu ; Sho Igaya ; Makiko Shimizu ; Norio Shibata ; Masato Nakamura ; Goutam Chowdhury ; F. Peter Guengerich
• 刊名：Chemical Research in Toxicology
• 出版年：2011
• 出版时间：March 21, 2011
• 年：2011
• 卷：24
• 期：3
• 页码：287-289
• 全文大小：685K
• 年卷期：v.24,no.3(March 21, 2011)
• ISSN：1520-5010

文摘

Metabolism of the teratogen thalidomide is proposed to be relevant to its toxicological action. We demonstrated the formation of the glutathione (GSH) conjugate of (R)-5-hydroxythalidomide in vivo in chimeric NOD-scid IL2Rg^null mice with humanized livers (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.