α-Tocopherol, ascorbic acid, and β-carotene protect against oxidative stress but reveal no direct influence on p53 expression in rats subjected to stress

We hypothesized that alpha-tocopherol, ascorbic acid, and beta-carotene, either applied individually or in combination, would modulate redox homeostasis and affect the regulation of genes involved in DNA repair under stress conditions. To test this hypothesis, we analyzed the influence of these vitamins, either supplied individually or in combination, on the plasma lipid peroxide level and the hepatic level of 8-hydroxy-2'-deoxyguanosine in rats. We also evaluated the expression of p53 and Mdm2 protein in the intestinal epithelium, as these proteins are involved in the cellular regulation of DNA damage repair. Male Wistar rats (n = 112) were supplemented with a-tocopherol (2 mg), ascorbic acid (12 mg), and beta-carotene (1 mg), both individually and in combination, for 14 days; 32 control rats were treated with placebo. Half of the animals in each group (n = 8) were subjected to 15-minute treadmill running at 20 m/min to cause exercise-induced oxidative stress. A statistically significant reduction in lipid peroxide levels was observed in the plasma of rats subjected to exercise and given 2 or 3 of the antioxidants (P < .0001). Exercise, as well as coadministration of the antioxidants, had no significant effect on the amount of DNA damage. Downward trends in the level of p53 protein expression were observed both in exercised and nonexercised animals, especially when the studied vitamins were administered in combination. Our findings suggest that alpha-tocopherol, ascorbic acid, and beta-carotene, when given concurrently, have primarily antioxidant effects on lipids under stress but do not significantly affect the regulation of p53 gene expression. (C) 2013 Elsevier Inc. All rights reserved.