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Titolo:
Comparative mechanism and toxicity of tetra- and dithiomolybdates in the removal of copper
Autore:
Ogra, Y; Komada, Y; Suzuki, KT;
Indirizzi:
Chiba Univ, Fac Pharmaceut Sci, Chiba 2638522, Japan Chiba Univ Chiba Japan 2638522 Fac Pharmaceut Sci, Chiba 2638522, Japan
Titolo Testata:
JOURNAL OF INORGANIC BIOCHEMISTRY
fascicolo: 3, volume: 75, anno: 1999,
pagine: 199 - 204
SICI:
0162-0134(19990630)75:3<199:CMATOT>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
WILSON DISEASE GENE; LEC RATS; ATX1 GENE; TETRATHIOMOLYBDATE; CERULOPLASMIN; LIVER; METALLOTHIONEIN; EXPRESSION; PENICILLAMINE; MOLYBDENUM;
Keywords:
tetrathiomolybdate; copper; Wilson disease; sulfide; LEC rats;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Ogra, Y Chiba Univ, Fac Pharmaceut Sci, Chiba 2638522, Japan Chiba Univ Chiba Japan 2638522 rmaceut Sci, Chiba 2638522, Japan
Citazione:
Y. Ogra et al., "Comparative mechanism and toxicity of tetra- and dithiomolybdates in the removal of copper", J INORG BIO, 75(3), 1999, pp. 199-204

Abstract

Tetrathiomolybdate (TTM) can be used as a specific chelator to remove copper (Cu) accumulating in the form bound to metallothionein (MT) in the livers of Wilson disease patients and Long-Evans rats with a cinnamon-like coat color (LEC rats). However, an adverse effect, hepatotoxicity, was observed occasionally on its clinical application. The mechanism underlying the adverse effect of TTM has been studied in comparison with dithiomolybdate (DTM), and a safer and more effective therapy by TTM was proposed based on the mechanism. The activity of glutamic-pyruvic transaminase (GPT) in serum was shown to increase significantly on the treatment of Wistar rats with sulfide produced through hydrolytic degradation of TTM and DTM, the latter being more easily degraded. The hydrolytic degradation of TTM was enhanced under acidic conditions. Cu in Cu-containing enzymes such as Cu,Zn-superoxide dismutase (SOD) in liver and ceruloplasmin (Cp) in plasma was decreased by excessive thiomolybdates, the Cu being found in the plasma in the form of a Cu/thiomolybdate/albumin complex. The decreased amounts of Cu in SOD and Cp were explained by the sequestration of Cu from their chaperones by thiomolybdates rather than the direct removal of Cu from the enzymes. Although both TTM and DTM remove Cu from MT, DTM is not appropriate as a therapeutic agent for Wilson disease due to its easy hydrolysis and production of sulfide. (C) 1999 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 19:22:54