Loading…

Thiol-induced reduction of antimony(V) into antimony(III): a comparative study with trypanothione, cysteinyl-glycine, cysteine and glutathione

Gluthathione (GSH) has been previously shown to promote the reduction of pentavalent antimony (Sb(V)) into the more toxic trivalent antimony (Sb(II)) in the antimonial drug, meglumine antimonate. However, this reaction occurred at acidic pH (pH 5) but not at the pH of the cytosol (pH 7.2) in which G...

Full description

Saved in:
Bibliographic Details
Published in:Biometals 2003-09, Vol.16 (3), p.441-446
Main Authors: Ferreira, Claúdio dos Santos, Martins, Patricia Silveira, Demicheli, Cynthia, Brochu, Christian, Ouellette, Marc, Frézard, Frédéric
Format: Article
Language:English
Subjects:
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Gluthathione (GSH) has been previously shown to promote the reduction of pentavalent antimony (Sb(V)) into the more toxic trivalent antimony (Sb(II)) in the antimonial drug, meglumine antimonate. However, this reaction occurred at acidic pH (pH 5) but not at the pH of the cytosol (pH 7.2) in which GSH is encountered. The aim of the present study was to further characterize the reaction between thiols and antimonial drugs, addressing the following aspects: (i) the reducing activity of cysteine (Cys) and cysteinyl-glycine (Cys-Gly), expected to be the predominant thiols in the acidic compartments of mammalian cells; (ii) the reducing activity of trypanothione (T(SH)2), the main intracellular thiol in Leishmania parasites; (iii) the influence of the state of complexation of Sb(V) on the rate of Sb(V) reduction. We report here that Cys, Cys-Gly and T(SH)2 did promote the reduction of Sb(V) into Sb(III) at 37 degrees C. Strikingly, the initial rates of reduction of Sb(V) were much greater in the presence of Cys-Gly, Cys and T(SH)2 than in the presence of GSH. These reactions occurred at both pH 5 and pH 7 but were favored at acidic pH. Moreover, our data shows that Sb(V) is reduced more slowly in the form of meglumine antimonate than in its non-complexed form, indicating that the complexation of Sb(V) tends to slow down the rate of its reduction. In conclusion, our data supports the hypothesis that Sb(V) is reduced in vivo by T(SH)2 within Leishmania parasites and by Cys or Cys-Gly within the acidic compartments of mammalian cells.
ISSN:0966-0844
1572-8773
DOI:10.1023/A:1022823605068