title: In vitro interactions of thallium with components of the glutathione-dependent antioxidant defence system.
abstract: We investigated the hypothesis that thallium (Tl) interactions with the glutathione-dependent antioxidant defence system could contribute to the oxidative stress associated with Tl toxicity. Working in vitro with reduced glutathione (GSH), glutathione reductase (GR) or glutathione peroxidase (GPx) in solution, we studied the effects of Tl+ and Tl3+ (1-25 microM) on: (a) the amount of free GSH, investigating whether the metal binds to GSH and/or oxidizes it; (b) the activity of the enzyme GR, that catalyzes GSH regeneration; and (c) the enzyme GPx, that reduces hydroperoxide at expense of GSH oxidation. We found that, while Tl+ had no effect on GSH concentration, Tl3+ oxidized it. Both cations inhibited the reduction of GSSG by GR and the diaphorase activity of this enzyme. In addition, Tl3+ per se oxidized NADPH, the cofactor of GR. The effects of Tl on GPx activity depended on the metal charge: Tl+ inhibited GPx when cumene hydroperoxide (CuOOH) was the substrate, while Tl(3+)-mediated GPx inhibition occurred with both substrates. The present results show that Tl interacts with all the components of GSH/GSSG antioxidant defence system. Alterations of this protective pathway could be partially responsible for the oxidative stress associated with Tl toxicity.
authors.affiliation: Department of Biological Chemistry-IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956 (C1113AAD), Buenos Aires, Argentina.
authors.forename: Marcela S
authors.initials: MS
authors.lastname: Villaverde
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Hanzel
authors.forename: Sandra V
authors.initials: SV
authors.lastname: Verstraeten
mesh_terms: D000975:Antioxidants / Q000032:analysis / Q000737:chemistry*; D001555:Benzene Derivatives / Q000032:analysis / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D005978:Glutathione / Q000032:analysis / Q000737:chemistry*; D019803:Glutathione Disulfide / Q000032:analysis / Q000737:chemistry*; D005979:Glutathione Peroxidase / Q000032:analysis / Q000737:chemistry*; D005980:Glutathione Reductase / Q000032:analysis / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000032:analysis / Q000737:chemistry; D009249:NADP / Q000032:analysis / Q000737:chemistry; D010084:Oxidation-Reduction; D013793:Thallium / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D001555:Benzene Derivatives; D002412:Cations; D009249:NADP; D013793:Thallium; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; C007164:cumene hydroperoxide; D019803:Glutathione Disulfide