ミヤヤマ タカミツ   Takamitsu Miyayama
  宮山 貴光
   所属   医学部 医学科
   職種   助教
論文種別 原著
言語種別 英語
査読の有無 査読有り
表題 Effect of glutathione depletion on removal of copper from LEC rat livers by tetrathiomolybdate
掲載誌名 正式名:Journal of Inorganic Biochemistry
略  称:J Inorg Biochem
ISSNコード:1873-3344 (Electronic)0162-0134 (Linking)
巻・号・頁 104(8),858-62頁
著者・共著者 OGRA Yasumitsu†*, MIYAYAMA Takamitsu, ANAN Yasumi
発行年月 2010/08
概要 Tetrathiomolybdate (TTM) is a powerful and selective copper (Cu) chelator that is used as a therapeutic agent for Wilson disease. TTM is the sole agent that can remove Cu bound to metallothionein (MT) in the livers of Long-Evans rats with a cinnamon-like coat color (LEC rats). However, the administration of excess TTM causes the deposition of Cu and molybdenum (Mo) in the liver. In the present study, the effect of hepatic glutathione (GSH) depletion on the removal of Cu from the livers of LEC rats was evaluated to establish an effective therapy by TTM. Pretreatment with l-buthionine sulfoximine (BSO), a depletor of GSH in vivo, reduced the amounts of Cu and Mo excreted into both the bile and the bloodstream, and increased the amounts of Cu and Mo deposited in the livers of LEC rats in the form of an insoluble complex 4h after the TTM injection. The results suggest that GSH depletion creates an oxidative environment in the livers of LEC rats, and the oxidative environment facilitates the insolubilization of Cu and Mo in the livers of LEC rats after the TTM injection. Therefore, the effect of TTM on the removal of Cu from the liver was reduced in the oxidized condition. Wilson disease patients and LEC rats develop liver injury caused by oxidative damage. From a clinical viewpoint, increasing in the GSH concentration is expected to enhance the effect of TTM.
DOI 10.1016/j.jinorgbio.2010.04.001S0162-0134(10)00091-7 [pii]
文献番号 20427090