EFFECT OF THE ANTIOXIDANT PROBUCOL ON TRANSPLANT ARTERIOSCLEROSIS IN AORTA ALLOGRAFTED RABBITS

The attenuation of atherogenesis by oral probucol treatment, demonstra ted in several animal studies, has been attributed to the antioxidativ e property of probucol. It is thought that probucol, by inhibiting oxi dation of low density lipoproteins (LDL), decreases the uptake of LDL into monocytes, and thereby reduces the development of foam cells and fatty streaks. Also, the neointimal proliferation seen after balloon i njury has been attenuated by treatment with probucol, Since foam cells and neointimal proliferation are both important elements of transplan t arteriosclerosis, we have investigated whether probucol might also r etard the development of experimental transplant arteriosclerosis. The thoracic aorta from one rabbit was transplanted as a bypass graft ont o the abdominal aorta of another rabbit. Nine rabbits were treated wit h Ig probucol per day and seven animals were treated with vehicle. Aft er a recovery period of 2 weeks, all rabbits were clamped at a human l evel of plasma cholesterol (6 to 7 mmol/l) for a period of 3 weeks. Th e amount of dietary cholesterol necessary for this clamping tended to be higher in probucol treated than in vehicle-treated rabbits. The dis tribution of plasma cholesterol between lipoprotein classes was simila r in the two groups, except for the concentration of high density lipo proteins (HDL), which was significantly lowered by probucol. Probucol markedly decreased the susceptibility of LDL and intermediate density lipoprotein plus very low density lipoprotein (IDL+VLDL) particles to oxidation, as measured by the production of conjugated dienes when add ing CU2+, Despite this, the development of transplant arteriosclerosis as well as the number of macrophages in the neointima were not signif icantly different in the aortic allografts from the two groups. These results suggest that antioxidative agents do not retard the developmen t of experimental transplant arteriosclerosis. (C) 1995 Academic Press Limited.