Glutathione metabolism is impaired in vitro by thallium(III) hydroxide.
The possibility that Tl(OH)3, the main Tl3+ specie present in water solutions, could interfere with the normal functioning of the glutathione-dependent antioxidant defense system was investigated. For this purpose, we used both the purified components of this system and rat brain cytosolic fractions. Tl(OH)3 (1-25 microM) significantly decreased the content of reduced glutathione (GSH) in both experimental systems, caused by GSH oxidation. In the same range of concentrations Tl(OH)3 inhibited glutathione peroxidase (GPx) activity in both models, using cumene hydroperoxide as the substrate. No alterations in the capacity of GPx activity to metabolize H2O2 were observed. Both in purified GR as well as in the cytosolic fraction, Tl(OH)3 (1-5 microM) inhibited GR activity, with a partial recovery of the activity at higher concentrations. While Tl(OH)3 inhibited the GR diaphorase activity of purified GR, in a concentration (1-25 microM) dependent manner, this effect was only observed in the cytosolic fractions at the highest concentration assessed (25 microM). Results indicate that, similarly to previous findings for Tl+ and Tl3+, Tl(OH)3 also alters the glutathione-dependent antioxidant defense system. The observed alterations of this important antioxidant protective pathway by the major Tl3+ specie in water solutions could be one mechanism involved in the oxidative stress associated to Tl-intoxication.
Hanzel
Cecilia E
CE
Department of Biological Chemistry-IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
Villaverde
Marcela S
MS
Verstraeten
Sandra V
SV
D000818:Animals; D001921:Brain; D001923:Brain Chemistry; D002374:Catalase / Q000378:metabolism; D002458:Cell Fractionation; D003600:Cytosol / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013793:Thallium / Q000633:toxicity*
D004791:Enzyme Inhibitors; C497385:thallium(III) hydroxide; D009249:NADP; D013793:Thallium; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione