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Article

High Levels of Dietary Vitamin E Do Not Replace Cellular Glutathione Peroxidase in Protecting Mice from Acute Oxidative Stress^{1 ,2}

Department of Animal Science, Cornell University, Ithaca, NY 14853 and ^* Department of Biomedical Science, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331

³To whom correspondence should be addressed.

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 7500 mg all-rac--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--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 F₂-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.

KEY WORDS: • glutathione peroxidase • vitamin E • selenium • F₂-isoprostanes • mice

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