Takamitsu Miyayama    Department   School of Medicine, School of Medicine    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Effect of glutathione depletion on removal of copper from LEC rat livers by tetrathiomolybdate
Journal	Formal name：Journal of Inorganic Biochemistry Abbreviation：J Inorg Biochem ISSN code：1873-3344 (Electronic)0162-0134 (Linking)
Volume, Issue, Page	104(8),pp.858-62
Author and coauthor	OGRA Yasumitsu†*, MIYAYAMA Takamitsu, ANAN Yasumi
Authorship	2nd author
Publication date	2010/08
Summary	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]
Document No.	20427090