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-blind, 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.
Cristol
L S
LS
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas 75235.
Jialal
I
I
Grundy
S M
SM
D004311:Double-Blind Method; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011341:Probucol / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies
D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011341:Probucol