Effects of probucol on experimental atherosclerosis in cholesterol-fed rabbits were studied. Male New Zealand white rabbits weighing 1.5kg were divided in 4 groups. Group 1 rabbits (n=17) received 200mg of probucol and 400mg of cholesterol per kg body weight in the chow. Animals in group 2 (n=12) were fed the same doses of cholesterol but without probucol. Those in group 3 (n=11) were fed the same dosage of probucol as group 1 but without cholesterol. Group 4 (n=12) rabbits were fed standard chow. Serum lipid concentrations were determined every 4 weeks. 16 weeks after the start of the experiment, the animals were sacrificed and the percentage surface area of visible plaques in the thoracic aorta was measured. Separate tissues from the thoracic aorta and cornea were used for microscopic study.
The following results were obtained:
1) Serum total cholesterol in group 1 and 2 was significantly higher than in group 3 and 4. But the difference between group 1 and 2 was not significant (Table 1).
2) Percentage surface area of plaques in group 1 (33±22%) was significantly lower than in group 2 (75±23%) (p<0.001) (Fig. 1).
3) Histological study revealed a decrease in number of foam cells and spindle cells in atheromatous plaque in group 1 as compared with group 2 (Fig. 3-A, B).
4) Corneal opacity with angiogenesis was observed in animals in group 1, but not in groups 3 and 4. In group 2 animals, corneal arcus was observed (Fig. 4-A, B, C).
5) Histologically the corneal opacity in group 1 had marked angiogenesis with perivascular foam cells in the all layers of corneal stroma (Fig. 5A). The corneal arcus in group 2 had less marked angiogenesis with foam cells in just the anterior portion of corneal stroma (Fig. SB). In both groups sudanophilia was located in foam cell bodies (Fig. 5-E, F).
Thus, probucol prevents the progression of atherosclerosis without lowering serum total cholesterol. It may be concluded that probucol has a benefit in preventing atherosclerosis but some attention should be paid to the generation of ocular lesions in the experimental hypercholesterolemia.
