High levels of dietary vitamin E do not replace cellular glutathione peroxidase in protecting mice from acute oxidative stress.
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.
Cheng
W H
WH
Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
Valentine
B A
BA
Lei
X G
XG
D000818:Animals; D004032:Diet; D004178:Diquat / Q000037:antagonists & inhibitors / Q000633:toxicity; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000627:therapeutic use*; D006540:Herbicides / Q000037:antagonists & inhibitors / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*; D013045:Species Specificity; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage* / Q000627:therapeutic use
D006540:Herbicides; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D004178:Diquat; D005979:Glutathione Peroxidase; D012643:Selenium; D010269:Paraquat