[show abstract][hide abstract] ABSTRACT: Hypercholesterolemic diets are associated with oxidative stress that may contribute to hypercholesterolemia by adversely affecting enzymatically-generated oxysterols involved in cholesterol homeostasis. An experiment was conducted to examine whether the cholesterol-lowering effects of the antioxidants selenium and α-tocopherol were related to hepatic oxysterol concentrations. Four groups of male Syrian hamsters (n = 7-8) were fed high cholesterol and saturated fat (0.46% cholesterol, 14.3% fat) hypercholesterolemic semi-purified diets: 1) Control; 2) Control + α-tocopherol (67 IU all-racemic-α-tocopheryl-acetate/kg diet); 3) Control + selenium (3.4 mg selenate/kg diet); and 4) Control + α-tocopherol + selenium. Antioxidant supplementation was associated with lowered plasma cholesterol concentrations, decreased tissue lipid peroxidation and higher hepatic oxysterol concentrations. A second experiment examined the effect of graded selenium doses (0.15, 0.85, 1.7 and 3.4 mg selenate/kg diet) on mRNA expression of the oxysterol-generating enzyme, hepatic 27-hydroxylase (CYP27A1, EC 184.108.40.206), in hamsters (n = 8-9) fed the hypercholesterolemic diets. Supplementation of selenium at 3.4 mg selenate/kg diet was not associated with increased hepatic 27-hydroxylase mRNA. In conclusion, the cholesterol lowering effects of selenium and α-tocopherol were associated with increased hepatic enzymatically generated oxysterol concentrations, which appears to be mediated via improved antioxidant status rather than increased enzymatic production.
[show abstract][hide abstract] ABSTRACT: The aim of the present work was to test the effects of large-dose supplementation of vitamin E (Vit E) and selenium (Se), either singly or in combination, on fish oil (FO)-induced tissue lipid peroxidation and hyperlipidemia. The supplementation of Se has been shown to lower blood cholesterol and increase tissue concentrations of the antioxidant glutathione (GSH); however, the effects of Se supplementation, either alone or in combination with supplemental Vit E, on FO-induced oxidative stress and hyperlipidemia have not been studied. Male Syrian hamsters received FO-based diets that contained 14.3 wt% fat and 0.46 wt% cholesterol supplemented with Vit E (129 IU D-alpha-tocopheryl acetate/kg diet) and/or Se (3.4 ppm as sodium selenate) or that contained basal requirements of both nutrients. The cardiac tissue of hamsters fed supplemental Se showed increased concentrations of lipid hydroperoxides (LPO) but decreased oxidized glutathione (GSSG) concentrations. The higher concentrations of LPO in the hearts of Se-supplemented hamsters were not lowered with concurrent Vit E supplementation. In the liver, Se supplementation was associated with higher Se-dependent glutathione peroxidase activity and an increase in the GSH/GSSG ratio, whereas a lower hepatic non-Se-dependent glutathione peroxidase activity was seen with Vit E supplementation. Supplemental intake of Se was associated with lower plasma concentrations of total cholesterol and low density lipoprotein cholesterol plus very low density lipoprotein cholesterol. In view of the pro-oxidative effects of Se supplementation on cardiac tissue, a cautionary approach needs to be taken regarding the plasma lipid-lowering properties of supplemental Se.