title: Effects of tetrathiomolybdate and penicillamine on brain hydroxyl radical and free copper levels: a microdialysis study in vivo.
abstract: Wilson disease is an inherited disorder of excessive copper accumulation. The commonly used drug d-penicillamine (PA) or trientine both cause a high incidence (10-50%) of neurological worsening, which rarely occurs with tetrathiomolybdate (TM) treatment. To investigate the mechanisms of neurologic deterioration after the initiation of chelation therapy, brain hydroxyl radical and free copper were assessed in vivo in this study. On days 3, 7, 14, and 21 after PA or TM administration, striatal hydroxyl radical levels of both TX mice and controls were assessed by terephthalic acid (TA) combined with microdialysis and high-performance liquid chromatography (HPLC). Within the same microdialysis samples, free copper was measured by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that both hydroxyl radical and free copper markedly increased in the striatum of TX mice during PA administration but were not elevated when administering TM. These results suggested that the further increased free copper in the brain and oxidative stress caused by some chelators might contribute to the neurological deterioration.
authors: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Ji-Wei
authors: JW
authors: Zhang
authors: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Jun-Xiu
authors: JX
authors: Liu
authors: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; Department of Neurology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors: Hai-Man
authors: HM
authors: Hou
authors: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Ding-Bang
authors: DB
authors: Chen
authors: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Li
authors: L
authors: Feng
authors: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Chao
authors: C
authors: Wu
authors: Department of Neurology, Luoyang Central Hospital, Affiliated to Zhengzhou University, Luoyang, China.
authors: Li-Ting
authors: LT
authors: Wei
authors: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address: lxh59xyh@sina.com.
authors: Xun-Hua
authors: XH
authors: Li
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002614:Chelating Agents / Q000009:adverse effects / Q000494:pharmacology; D003300:Copper / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D006527:Hepatolenticular Degeneration / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017551:Microdialysis; D008982:Molybdenum / Q000009:adverse effects / Q000494:pharmacology*; D010396:Penicillamine / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D002614:Chelating Agents; D017665:Hydroxyl Radical; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D010396:Penicillamine
keywords: Free copper; Hydroxyl radical; In vivo; Tetrathiomolybdate; Wilson disease; d-penicillamine