EFFECT OF LOW-DOSE PROBUCOL THERAPY ON LDL OXIDATION AND THE PLASMA-LIPOPROTEIN PROFILE IN MALE-VOLUNTEERS

The effect of 4 months of low-dose probucol treatment (250 mg/day) on LDL oxidation and on plasma-HDL cholesterol was studied in a prospective, double-blinded, randomized, placebo-controlled trial involving 26 male volunteers. LDL samples isolated at baseline and at 4 months were subjected to in vitro tests of LDL oxidation, involving copper-catalyzed, time-course experiments. For the placebo group, LDL oxidation did not significantly change over the 4-month period. However, in the probucol group, LDL oxidation was significantly inhibited at 4 months, as evidenced by assays measuring conjugated diene formation, lipid peroxide production and altered electrophoretic mobility of oxidized LDL. In fact, in the probucol group the 'lag-phase' of oxidation was prolonged 2.7-fold. Neither probucol nor placebo had a significant effect on plasma HDL-cholesterol: in the probucol group HDL-cholesterol fell from 37.7 +/- 7.4 mg/dl to 34.2 +/- 8.3 mg/dl (percentage decrease -8.9), while in the placebo group plasma HDL-cholesterol levels were 42.4 +/- 8.3 mg/dl and 40.9 +/- 7.0 mg/dl at baseline and 4 months (percentage decrease -2.7). Therefore, a low dose of probucol (250 mg/day) given daily seems to afford protection against the oxidative modification of LDL, and does not appear to exert any substantial effect on the plasma lipoprotein profile.