EFFECT OF PROBUCOL AND A NEW ANALOG ON CHOLESTEROL AND LIPOPROTEIN METABOLISM IN CULTURED RABBIT HEPATOCYTES

A comparative study of the effect of probucol and its new analog K5 on cholesterol and lipoprotein metabolism was carried out in cultured ra bbit hepatocytes. At a concentration of 100 mu M, probucol inhibited t he incorporation of [2-C-14]acetate into cholesterol by 24-28%. Unlike probucol, K5 did not affect the synthesis of cholesterol at the same concentration but inhibited secretion of apolipoprotein B (apo B)-cont aining particles by hepatocytes to the cultivation medium by 44-55%. N o effect of either of the tested compounds on the level of incorporati on of [C-14]leucine into total cell protein could be observed. Probuco l at a concentration of 100 mu M stimulated specific uptake of I-125-l abeled low density lipoproteins (LDL) by 29-64% and enhanced glycoholi c and taurocholic acid synthesis by 29-93% and 45-77%, respectively; t otal bile acid synthesis from [4-C-14]cholesterol of the second fracti on of high density lipoproteins (HDL(2)) increased by 25-36%. However, the K5 did not noticeably affect these processes. These results confi rm that the main mechanisms of the hypocholesterolemic effect of probu col at the level of the liver can involve the enhancement of the speci fic uptake of LDL by hepatocytes and stimulation of bile acid synthesi s together with a moderate probucol-induced decrease in cholesterol sy nthesis. The observed decrease in secretion of apo B-containing partic les by hepatocytes induced by the new probucol analog is of definite i nterest because this can form the basis for its possible hypocholester olemic effect.