The main objectives of this investigation were to determine if (i) SDG produces regression of hypercholesterolemic atherosclerosis; (ii) regression is associated with reduction in serum lipids; and (iii) regression is associated with reduction in oxidative stress. In the regression phase of the present study, SDG treatment with regular diet for 2 months (Group IV) and for 4 months (Group V) following the high cholesterol diet reduced the atherosclerotic lesions by 24% and 45%, respectively, compared to the rabbits on regular diet following high cholesterol diet (Group III) indicating that there was no progression in atherosclerosis in Groups IV and V. Decreases in the extent of atherosclerosis with SDG for 4 months were greater than with SDG for 2 months, suggesting that a longer duration of treatment with SDG would be more beneficial than shorter duration of treatment. SDG in this study reduced serum and aortic MDA levels, indicating
a decrease in the levels of reactive oxygen species. Thus, a high cholesterol diet induces atherosclerosis which is associated with an increase in oxidative stress and hypercholesterolemia. Regular diet with or without SDG following a high cholesterol diet reduces the serum lipids to a similar extent, however regular diet accelerated the atherosclerosis. SDG with normal diet prevented the regular diet-induced progression of atherosclerosis, which was associated with a reduction in aortic oxidative stress.
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.
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