Dietary beta-carotene and alpha-tocopherol combination does not inhibit atherogenesis in an apoE-deficient mouse model

Although lipid oxidation plays a major role in atherogenesis, the role of a ntioxidants in the prevention and treatment of the process is not clear. Ap olipoprotein (apo) E-deficient mice develop spontaneous atherosclerotic les ions in major arteries. The presence of oxidized lipoprotein epitopes in th e lesion suggests that oxidation reactions are involved in atherogenesis in this mouse model, but the inhibitory effect of antioxidants on atherogenes is in the model is controversial. To test the effect of dietary antioxidant s on atherogenesis, male apoE-deficient mice (n = 15) were fed a standard c how diet supplemented with 0.05% alpha-tocopherol and 0.05% all-trans beta- carotene. A control group (n = 15) received no antioxidant supplement. At t he end of the trial, mice consuming vitamins had 5x more plasma vitamin E b ut undetectable beta-carotene levels. However, liver levels of the beta-car otene metabolite, retinyl palmitate, were higher in antioxidant-treated mic e compared with control mice. The antioxidants had no effect on lipoprotein or on plasma anti-oxidatively modified low density lipoproteins (anti-oxLD L) antibody levels. The vitamins had a small but insignificant effect on li poprotein resistance to ex vivo oxidation, determined by a longer lag perio d of conjugated diene formation. Atherosclerosis, determined by the lesion size at the aortic sinus, was insignificantly suppressed in antioxidant-tre ated mice (mean area +/- SE, 20 000 +/- 7129 versus 13 281 +/- 5861 mu m(2) ; P = 0.40). The aortic atherosclerotic lesion area was similar in both exp erimental groups (2.55 +/- 0.65% and 2.08 +/- 0.5% of total aortic area in the control and antioxidant group, respectively; P = 0.58). The results of the current study suggest that moderate levels of synthetic antioxidant vit amins have no effect on atherogenesis in apoE-deficient mice.