THE EFFECTS OF PROBUCOL ON THE LEVELS, STRUCTURE, COMPOSITION AND METABOLISM OF PLASMA-LIPOPROTEIN IN RATS

The effects of probucol administration on the levels, structure, composition and metabolism of plasma lipoproteins were determined in male rats. Probucol caused a 25% decrease of plasma cholesterol and a 20% decrease of plasma triacylglycerols. The effect was more pronounced on lipoproteins of density less than 1.063 g/ml (-35%) than on density greater than 1.063 g/ml (-21%). The density of LDL, HDL-1 and HDL-2 separated by ultracentrifugation on a zonal rotor was shifted towards a higher density. The content of cholesteryl esters increased in VLDL and LDL and decreased in HDL-1 and HDL-2. LDL, HDL-1 and HDL-2 were relatively enriched with proteins. The intravascular metabolism of I-125-labeled apo A-I was identical in control and probucol-treated rats with a circulating half-lifetime of 9.5 h. The circulating half-lifetime of LDL labeled biosynthetically with [H-3]cholesteryl esters was also identical, 6.5 h. The circulating half-lifetime of [H-3]cholesteryl esters in HDL-2, in contrast, was 9.5 h in control rats and 7.5 h in probucol-treated animals. Plasma cholesterol ester transfer activity was almost undectectable in either control or probucol treated animals. The investigation demonstrates a pronounced effect of probucol on plasma lipid and lipoprotein levels in rats, on cholesterol ester distribution between lipoproteins and on lipoprotein transport rates in the plasma. These effects may contribute to the anti-atherogenetic action of probucol.