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 (20mg x kg body wt(-1) x 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.