Atheroprotective effects of pure tocotrienol supplementation in the treatment of rabbits with experimentally induced early and established atherosclerosis
Sammanfattning
Background: Atherosclerosis is the main cause of coronary artery disease -related deaths worldwide. The
atheroprotective properties of pure tocotrienols (T3) in the absence of alpha-tocopherol (a-TCP) in vitamin E
has not been extensively examined.
Aim: To determine the atheroprotective properties of T3 in early and established atherosclerosis rabbits.
Methods: Thirty New Zealand white rabbits were divided into two groups, B1 and B2 which represent early [fed
1% high cholesterol diet (HCD) for 2 weeks] and established (fed 1% HCD for 8 weeks) atherosclerosis. Each
group was subdivided into three intervention arms: 1) T3-4 mg/kg, 2) T3-15 mg/kg and 3) vehicle without T3
(T3 negative) for 8 weeks. Serial fasting blood samples were obtained for lipid profile, and whole lengths of
aorta were used to determine tissue markers of endothelial activation, inflammation and plaque stability.
Results: In B1, atherosclerotic lesion in T3-4 mg/kg group was significantly reduced (p = 0.008), while aortic
tissue expression of vascular cellular adhesion molecule 1 (VCAM-1), interleukin-6 (IL-6) and matrix
metalloproteinase (MMP-12) was reduced in T3-4 mg/kg compared to T3-negative rabbits group (0.2+0.1
vs. 28.5+3.1%; 3.0+1.6 vs. 14.0+1.7%; and 5.2+2.2 vs. 27.7+0.8%, respectively, p<0.05). T3-15 mg/kg group
showed reduction in VCAM-1, E-selectin, IL-6 and MMP-12 (3.9+1.9 vs. 28.5+3.1%; 10.3+0.5 vs.
59.8+8.5%; 2.6+1.7 vs. 14.0+1.7%; and 16.2+3.2 vs. 27.7 0.8%, respectively, p<0.05). In B2, T3-4 mg/kg
group reduced aortic tissue expression of intercellular adhesion molecule 1 (ICAM-1), E-selectin, IL-6, MMP-12
and MMP-9 compared to T3-negative rabbits group (29.9+2.4 vs. 55.3+1.3%; 26.7+1.5 vs. 60.5+7.6%;
15.7+0.7 vs. 27.7+4.8%; 34.8+2.7 vs. 46.5+3.4%; and 25.89+3.9 vs. 45.9+1.7%, respectively, p<0.05).
T3-15 mg/kg group showed reduced VCAM-1, ICAM-1, E-selectin, IL-6, MMP-12 and MMP-9 (20.5+3.3 vs.
35.6+2.5%; 24.9+1.3 vs. 55.3+1.3%; 29.9+6.7 vs. 60.5+7.6; 11.3+2.2 vs. 27.7+4.8%; 23.0+1.7 vs.
46.5+3.4%; and 17.6+1.9 vs. 45.9+1.7%, respectively, p<0.05.
Conclusion: These findings suggest the possible atheroprotective role T3 plays as an adjunct supplementation
to standard treatment in the prevention of CAD.