High-dose supplemental selenite to male Syrian hamsters fed hypercholesterolaemic diets alters Ldlr, Abcg8 and Npc1l1 mRNA expression and lowers plasma cholesterol concentrations.

The aim of the present study was to elucidate possible cholesterol-lowering mechanism(s) of high-dose supplemental Se in the form of selenite, a known hypocholesterolaemic agent. Male Syrian hamsters (four groups, ten per group) were fed semi-purified diets for 4 weeks containing 0.1 % cholesterol and 15 % saturated fat with selenite corresponding to varying levels of Se: (1) Se 0.15 parts per million (ppm), control diet; (2) Se 0.85 ppm; (3) Se 1.7 ppm; (4) Se 3.4 ppm. Lipids were measured in the bile, faeces, liver and plasma. The mRNA expression of several known regulators of cholesterol homeostasis (ATP-binding cassette transporters g5 (Abcg5) and g8 (Abcg8), 7-hydroxylase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, LDL receptor (LdLr) and Nieman-Pick C1-like 1 protein (Npc1l1)) were measured in the liver and/or jejunum. Oxysterols including 24-(S)-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol (27-OHC) were measured in the liver. Significantly lower total plasma cholesterol concentrations were observed in hamsters consuming the low (0.85 ppm) and high (3.4 ppm) Se doses. The two highest doses of Se resulted in decreased plasma LDL-cholesterol concentrations and increased mRNA levels of hepatic Abcg8, Ldlr and jejunal Ldlr. Higher hepatic 27-OHC and TAG concentrations and lower levels of jejunal Npc1l1 mRNA expression were noted in the 1.7 and 3.4 ppm Se-treated hamsters. Overall, Se-induced tissue changes in mRNA expression including increased hepatic Abcg8 and Ldlr, increased jejunal Ldlr and decreased jejunal Npc1l1, provide further elucidation regarding the hypocholesterolaemic mechanisms of action of Se in the form of selenite.

Antioxidant Supplements Improve Profiles of Hepatic Oxysterols and Plasma Lipids in Butter-fed Hamsters.

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 1.14.13.15), 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.

The effects of vitamin E and selenium intake on oxidative stress and plasma lipids in hamsters fed fish oil.

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.