Inhibition of expression of P-selectin by antioxidant in cholesterol-fed rats

Butylated hydroxytoluene (BHT) can inhibit experimental atherosclerosis in animals. Although the agent is an antioxidant, the exact mechanism of the reaction in atherosclerosis is still unknown. To investigate the effects of BHT on expression of P-selectin (PADGEM, GMP-140), intercellular adhesion molecule-1 (ICAM-1) and class II MHC (Ia) antigen, we proposed an experiment on rats. Male rats (n=18 per group) were fed either a normal cholesterol control diet, a normal cholesterol diet containing 0.5% BHT (BD), a high cholesterol diet containing 1.5% cholesterol and 0.1% sodium cholate (CD), or the CD diet containing 0.5% BHT (BCD). Rats were sacrificed after 3 days, and after 1, 2, 4, 10, and 17 weeks of dietary treatment. Although there was no gross or light microscopic atherosclerotic lesions, scanning electron microscopy revealed monocytic adhesion to aortic endothelium and mild endothelial injuries in CD and BCD groups. Immunohistochemically, the addition of BHT to a high cholesterol diet inhibited P-selectin expression but not in ICAM-1 and Ia antigen. These findings suggest that in rats, high cholesterol diets induce expression of ICAM-1, P-selectin and Ia antigen. In addition, the antiatherogenic effect of BHT may play a role in the inhibition of P-selectin.

Effect of Eicosapentaenioc acid and Butyrated hydroxyanisole on Hypercholestrolemic Diet Induced Atherogenesis in Rabbit

It has been suggested that the fish oil can reduce atherogenesis in humans and animals, and that peroxidation of lipoproteins may be a major factor causing atherosclerotic lesions. We tested these posibilities in rabbits fed an atherogenic diet by comparing the effect of a eicosapentaenoic acid(EPA: a major component of fish oil)supplement and a butyrated hydroxyanisole(BHA: antioxidant)diet supplement. Tweenty-eight young male New Zealand White rabbits were used in this study. The animals were divided by control, cholesterol fed only, cholesterol + EPA, and cholesterol + BHA groups. The experimental course lasted 12 weeks and animals were sacrificed periodically(2, 5, 8, 12weeks)for quantitative studies of aortic atherosclerosis using light and electron microscopy. Plasma cholesterol levels were determined and lipopreteins were separated periodically. The cholesterol fed only group showed an increased serum cholseterol level and atherosclerotic lesions from 5 weeks of experiments. The EPA supplement resulted in similiar serum cholesterol levels with cholesterol fed only group, but greater lesion than cholesterol fed only group. The BHA supplement resulted in higher serum cholesterol levels except VLDL-cholesterol than EPA supplement group. However, the atherosclerotic lesion was not increased. Our studies support the theory that oxidative modification of lipoproteins is important for the atherogenesis and antioxidant may have a protective effect. However, it failed to show antiatherogenesis effect of fish oil.