“Thallium alters glutathione-dependent antioxidant defense system.”

VILLAVERDE M.S.; HANZEL C.; VERSTRAETEN S.V.

Buenos Aires, Argentina.

Congreso; 12th Biennal Meeting of the International Society for Free Radical Research.; 2004

Free Radicals Society

THALLIUM ALTERS GLUTATHIONE-DEPENDENT ANTIOXIDANT DEFENSE SYSTEM. M. S. Villaverde1, C. E. Hanzel1 and S.V. Verstraeten1. 1Department of Biological Chemistry, IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 (C1113AAD), Buenos Aires, Argentina.             The hypothesis that thallium (Tl) interactions with the glutathione (GSH)-dependent antioxidant defenses could contribute to the oxidative stress associated with Tl-toxicity was investigated. Working with buffered solutions of reduced GSH, glutathione reductase (Gred) or glutathione peroxidase (GPx) we studied the effects of Tl+, Tl3+ and Tl(OH)3 (1-25 microM) on the concentration of free GSH, on GSH oxidation, and on the activity of the enzymes. Tl+ had no effect on reduced GSH concentration, while Tl3+ and Tl(OH)3 oxidized GSH. All the species inhibited the reduction of GSSG by GRed and the diaphoras4 activity of this enzyme. Tl3+ also oxidized NADPH, the cofactor of GRed. The effect of Tl on GPx activity depended on its speciation: Tl+ inhibited the enzyme when cumene hydroperoxide was the substrate, while Tl(OH)3 inhibited GPx in the presence of H2O2, and Tl3+ inhibited the reduction of botj substrates. The present results demonstrate that Tl interacts with all the components of GSH/GSSG antioxidant defense system suggesting that alterations of this antioxidant protective pathway can be involved in the oxidative stress condition associated with Tl intoxication. This work was supported by grants from the University of Buenos Aires (B405) Argentina and the Third World Academy of Science (01-350 RG/BIO/LA).