title: Antioxidant Supplements Improve Profiles of Hepatic Oxysterols and Plasma Lipids in Butter-fed Hamsters.
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 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.
authors: School of Dietetics and Human Nutrition, Macdonald Campus of McGill University, Ste-Anne-de-Bellevue, Quebec, Canada H9X 3V9.
authors: Johanne
authors: J
authors: Poirier
authors: Kevin A
authors: KA
authors: Cockell
authors: W M Nimal
authors: WM
authors: Ratnayake
authors: Kylie A
authors: KA
authors: Scoggan
authors: Nick
authors: N
authors: Hidiroglou
authors: Claude
authors: C
authors: Gagnon
authors: Hélène
authors: H
authors: Rocheleau
authors: Heidi
authors: H
authors: Gruber
authors: Philip
authors: P
authors: Griffin
authors: René
authors: R
authors: Madère
authors: Keith
authors: K
authors: Trick
authors: Stan
authors: S
authors: Kubow
keywords: glutathione; lipid hydroperoxide; selenium; sterol 27-hydroxylase mRNA; thiobarbituric acid-reading substances; tocopherols
references: Biol Trace Elem Res. 2000 Dec;77(3):273-85
references: 11204469
references: J Biol Chem. 1997 Feb 7;272(6):3137-40
references: 9013544
references: Lipids. 2008 Apr;43(4):383-90
references: 18335267
references: J Lipid Res. 2001 Apr;42(4):649-58
references: 11290837
references: Prog Lipid Res. 1996;35(2):93-132
references: 8944223
references: Cell Metab. 2007 Jan;5(1):73-9
references: 17189208
references: Cell. 1998 May 29;93(5):693-704
references: 9630215
references: J Nutr. 1978 Nov;108(11):1858-67
references: 712430
references: Cancer Epidemiol Biomarkers Prev. 2006 Aug;15(8):1479-84
references: 16896036
references: Lipids. 2002 Dec;37(12):1125-33
references: 12617464
references: Menopause. 2008 Jan-Feb;15(1):119-24
references: 18257145
references: J Clin Invest. 2002 Sep;110(6):725-30
references: 12235099
references: J Nutr. 2008 Jun;138(6):1179-81
references: 18492853
references: J Nutr. 2010 Jan;140(1):81-7
references: 19906812
references: Biol Trace Elem Res. 1995 Jan-Mar;47(1-3):343-7
references: 7779568
references: J Biol Chem. 1989 Apr 25;264(12):6863-9
references: 2708346
references: Cochrane Database Syst Rev. 2008 Apr 16;(2):CD007176
references: 18425980
references: Yakugaku Zasshi. 2001 Jan;121(1):93-6
references: 11201167
references: Atherosclerosis. 1975 Jul-Aug;22(1):47-61
references: 1156470
references: Int J Vitam Nutr Res. 1990;60(3):240-4
references: 2276881
references: Chem Phys Lipids. 1987 Nov-Dec;45(2-4):143-69
references: 3319225
references: J Lab Clin Med. 1967 Jul;70(1):158-69
references: 6066618
references: Mol Cell Biochem. 2006 Jan;282(1-2):75-82
references: 16317514
references: Int J Vitam Nutr Res. 2001 Nov;71(6):339-46
references: 11840837
references: Biol Res. 2006;39(2):307-19
references: 16874406
references: Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):266-71
references: 9874807
references: Lipids. 1996 Mar;31 Suppl:S87-90
references: 8729100
references: J Appl Toxicol. 2002 Nov-Dec;22(6):405-13
references: 12424744
references: Atherosclerosis. 1991 Mar;87(1):9-16
references: 1670289
references: Teratology. 1990 Oct;42(4):359-71
references: 2256000
references: Clin Sci (Lond). 2004 Jan;106(1):93-8
references: 12875648
references: Biochem Pharmacol. 1985 Mar 1;34(5):599-608
references: 3977940
references: Cardiovasc Res. 2005 Dec 1;68(3):425-32
references: 16099444
references: Cancer Biochem Biophys. 1995 Jun;15(1):41-7
references: 8536219
references: Gen Physiol Biophys. 1998 Mar;17(1):71-8
references: 9675557
references: Am Heart J. 1993 Apr;125(4):958-73
references: 8465768
references: Chem Biol Interact. 2006 May 15;161(1):49-56
references: 16581047
references: Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10588-93
references: 9380679
references: J Nutr Biochem. 2005 Dec;16(12):750-6
references: 16098731
references: Biochem Biophys Res Commun. 2005 Mar 11;328(2):432-41
references: 15694366
references: Drug Metab Dispos. 2006 Apr;34(4):513-20
references: 16434543
references: Food Chem Toxicol. 1985 Oct;23(10):945-7
references: 4065770
references: J Natl Cancer Inst. 2005 Jan 19;97(2):94-102
references: 15657339
references: Res Commun Chem Pathol Pharmacol. 1984 Dec;46(3):469-72
references: 6515133
references: J Lipid Res. 1983 Mar;24(3):303-15
references: 6842086
references: Lipids Health Dis. 2005 Nov 05;4:28
references: 16271152
references: Atherosclerosis. 1991 May;88(1):29-34
references: 1715163
references: Clin Chem. 1987 Feb;33(2 Pt 1):214-20
references: 3802504
references: Biometals. 2006 Oct;19(5):493-501
references: 16937255
references: Biochem Pharmacol. 1981 Dec 1;30(23):3217-23
references: 6119089
references: Indian J Biochem Biophys. 2001 Jun;38(3):176-9
references: 11693381
references: J Nutr. 1991 Sep;121(9):1331-40
references: 1880611
references: BMC Cardiovasc Disord. 2003 Jun 3;3:4
references: 12783625
references: Nutr J. 2003 May 12;2:3
references: 12773205
references: Lipids. 1996 Aug;31(8):839-47
references: 8869886
references: Arch Physiol Biochem. 1997 Oct;105(6):603-6
references: 9587653
references: J Biol Chem. 2001 Oct 19;276(42):38378-87
references: 11504730
references: Ann Nutr Metab. 1983;27(4):296-305
references: 6881915
references: Ann Nutr Metab. 1983;27(2):81-93
references: 6847126
references: Biol Trace Elem Res. 1994 Mar;40(3):247-53
references: 7517162
references: Br J Nutr. 1998 Jul;80(1):89-100
references: 9797648
references: J Biol Chem. 1992 Dec 15;267(35):25092-7
references: 1460011
references: Biol Trace Elem Res. 2000 Dec;77(3):231-9
references: 11204465
references: Biochim Biophys Acta. 1996 Jan 19;1299(2):216-22
references: 8555267