| 10539768 |
Cheng WH, Valentine BA, Lei XG: High levels of dietary vitamin E do not replace cellular glutathione peroxidase in protecting mice from acute oxidative stress. J Nutr. 1999 Nov;129(11):1951-7.
Our objective was to determine whether high levels of dietary vitamin E replaced the protection of the Se-dependent cellular glutathione peroxidase (GPX1) against paraquat- or diquat-induced acute oxidative stress in mice. Two experiments were conducted using GPX1 knockout [GPX1 (-/-)] mice and wild-type (WT) mice (n = 78/group). In Experiment 1, mice were fed torula yeast-based, Se-adequate (0.4 mg/kg as sodium selenite) diets + 0, 75, 750 or 7,500 mg all-rac-alpha-tocopheryl acetate for 5 wk before an intraperitoneal injection of 50 mg paraquat/kg body weight. In Experiment 2, mice were fed the diet + 0 or 750 mg all-rac-alpha-tocopheryl acetate for 5 wk and were killed 1 or 3 h after an injection of diquat at 12, 24 or 48 mg/kg. In Experiment 1, all mice died of the injection and there were 8- to 15-fold differences (P < 0.001) in survival times between the GPX1 (-/-) and the WT mice. Although increasing tocopheryl acetate from 0 to 750 mg/kg extended the survival time of the GPX1 (-/-) mice for 2 h (P = 0.06), the highest tocopheryl acetate level resulted in a decrease (P < 0.05) in survival time in the WT mice. The vitamin E-deficient GPX1 (-/-) mice had the highest concentration of hepatic thiobarbituric acid reacting substances. In Experiment 2, the diquat-induced formation of hepatic F (2)-isoprostanes was accelerated (P < 0.05) by vitamin E deficiency and was also affected by the GPX1 knockout. Diquat produced much greater (P < 0.01) dose-dependent increases in plasma alanine transaminase (ALT) activities in the GPX1 (-/-) than in the WT mice. Hepatic phospholipid hydroperoxide GPX activities were decreased (P < 0.05) by the diquat injection only in the vitamin E-deficient GPX1 (-/-) mice. Despite a potent inhibition of hepatic lipid peroxidation, high levels of dietary vitamin E do not replace the protection of GPX1 against the paraquat-induced lethality or the diquat-induced plasma ALT activity increase in mice. |
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