Abstract
Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is a lipid-lowering
and antioxidant agent. It suppresses the development of hypercholesterolemic atherosclerosis
in rabbits. It is however not known if SDG would produce regression of atherosclerosis.
The objectives of this study were to determine (i) if SDG produces regression of atherosclerosis;
(ii) if regression is associated with reduction in serum lipids, oxidative stress
or both; and (iii) if the duration of treatment has an effect on regression. Rabbits
were assigned to five groups: Group I, regular diet (control); Group II, 0.5% cholesterol
diet for 2 months (mo); Group III, same as Group II but followed by regular diet for
2 mo; Group IV, same as Group II and followed by regular diet with SDG (20 mg·kg body wt−1·day−1 PO) for 2 mo; and Group V, same as Group IV but SDG treatment for an additional 2 mo. Blood samples were collected from rabbits before and at monthly intervals thereafter
on their respective diet regimen for measurement of triglycerides (TG), total cholesterol
(TC), LDL-C, HDL-C and malondialdehyde (MDA), a lipid peroxidation product. At the
end of the protocol, the aorta was removed for assessment of atherosclerotic lesions,
aortic MDA and aortic chemiluminescence (Aortic-CL), a measure of antioxidant reserve.
MDA and Aortic-CL provide an index of oxidative stress. Increases in serum TG, TC,
LDL-C, HDL-C and the risk ratio TC/HDL-C in Group II were associated with an increase
in oxidative stress and development of atherosclerosis (57% of aortic intimal surface
covered with lesions). Serum lipids decreased to a similar extent in Groups III–V,
however atherosclerotic lesions were 84%, 63% and 44%, respectively in Groups III–V.
There were more atherosclerotic lesions in Group III (+48.9%) as compared to Group
II. The atherosclerotic lesions decreased by 24% and 45%, respectively in Groups IV
and V compared to Group III. The reduction in atherosclerotic lesions was associated
with a reduction in oxidative stress. These results suggest that (i) regular diet
following a high cholesterol diet accelerates atherosclerosis in spite of a decrease
in serum lipids; (ii) SDG treatment prevents the progression of atherosclerosis on
a regular diet following a high cholesterol diet; (iii) prevention of progression
is associated with a reduction of aortic oxidative stress and not with reductions
in serum lipids; (iv) a longer duration of treatment reduces the progression of atherosclerosis
to a greater extent, and tends to regress the atherosclerosis.
Keywords
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References
- Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E.Am Heart J. 1993; 125: 958-973
- Oxygen free radicals as a mechanism of hypercholesterolemic atherosclerosis: effects of Probucol.Int J Angiol. 1994; 3: 10-12
- Antioxidants in the prevention of human atherosclerosis.Circulation. 1992; 85: 2337-2344
- Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed.Circulation. 1999; 99: 1355-1362
- Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed.Atherosclerosis. 2005; 179: 269-275
- Suppression of hypercholesterolemic atherosclerosis by pentoxifylline and its mechanism.Atherosclerosis. 2007; 192: 313-322
- Suppression of oxidative stress as a mechanism of reduction of hypercholesterolemic atherosclerosis by cyclooxygenase inhibitors.Int J Angiol. 2003; 12: 13-23
- Flax seed as a source of alpha linolenic acid.J Am Coll Nutr. 1993; 12: 551
- High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans.Br J Nutr. 1993; 69: 443-453
Westcott ND, Muir AD. Process for Extracting Lignans from Flaxseed. US Patent 5,705,618, January 6, 1998.
- Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flaxseed.Mol Cell Biochem. 1997; 168: 117-123
- Antioxidant activity of secoisolariciresinol diglucoside-derived metabolites, secoisolariciresinol, enterodiol, and enterolactone.Int J Angiol. 2000; 9: 220-225
- Effect of lovastatin on suppression and regression of atherosclerosis in lipid-fed rabbits.J Cardiovasc Pharmacol. 1992; 19: 246-255
- A HMG-CoA reductase inhibitor improved regression of atherosclerosis in the rabbit aorta without affecting serum lipid levels: possible relevance of up-regulation of endothelial NO synthase mRNA.Biochem Biophys Res Commun. 1999; 259: 414-419
- A study of atherosclerosis regression in Macaca Mulatta.Exp Mol Pathol. 1984; 41: 96-118
- Combined effects of cholestyramine and probucol on regression of atherosclerosis in rhesus monkey aortas.Appl Pathol. 1983; 1: 89-96
- Role of oxyradicals in cardiovascular depression and cellular injury in hemorrhagic shock and reinfusion: effect of SOD and catalase.Circ Shock. 1994; 43: 79-94
- Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction.Anal Biochem. 1979; 95: 351-358
- Determination of serum proteins by means of biuret reaction.J Biol Chem. 1949; 177: 751-766
- Techniques for studying atherosclerotic lesions.Lab Invest. 1958; 7: 42-47
- Suppression of oxidative stress as a mechanism of reduction of hypocholesterolemic atherosclerosis by aspirin.J Cardiovasc Pharmacol Therapeut. 2003; 8: 61-69
- Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial.JAMA. 2006; 295: 1556-1565
- Possibilities of regression in arteriosclerosis.Z Gerontol Geriatr. 2001; 34: 466-469
- Antioxidant enzymes in hypercholesterolemia and effects of Vitamin E in rabbits.Atherosclerosis. 1993; 101: 135-144
- Oxidative injury to the vascular endothelium.Am J Med Sci. 1986; 292: 97-103
- Vitamin E inhibits low density lipoprotein-induced adhesion of monocytes to human aortic endothelial cells in vitro.Arterioscler Thromb Vasc Biol. 1997; 17: 429-436
- Reactive oxygen species are involved in shear stress-induced intracellular adhesion molecule-1 expression in endothelial cells.Arterioscler Thromb Vasc Biol. 1997; 17: 3570-3577
- Effects of long term cholesterol lowering on coronary atherosclerosis in patient risk factor subgroups: the Simvastatin/enalapril Coronary Atherosclerosis Trial (SCAT).Can J Cardiol. 2003; 19: 487-491
- Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL-lowering on atherosclerotic progression in carotid and femoral arteries.Circulation. 1995; 92: 1758-1764
- Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis.JAMA. 2007; 297: 499-508
- Antihypertensive activity of secoisolariciresinol diglucoside isolated from flaxseed: role of guanylate cyclase.Int J Angiol. 2004; 13: 7-14
- Molecular mechanisms of nitric oxide regulation. Potential relevance to cardiovascular disease.Circ Res. 1993; 73: 217-222
Article info
Publication history
Published online: October 01, 2007
Accepted:
July 27,
2007
Received in revised form:
July 10,
2007
Received:
May 22,
2007
Identification
Copyright
© 2007 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
