TY - JOUR
T1 - Effect of probucol dosage on plasma lipid and lipoprotein levels and on protection of low density lipoprotein against in vitro oxidation in humans
AU - Reaven, Peter D.
AU - Parthasarathy, Sampath
AU - Beltz, William F.
AU - Witztum, Joseph L.
PY - 1992
Y1 - 1992
N2 - To determine whether probucol's ability to confer antioxidant protection to low density lipoprotein (LDL) could be dissociated from its ability to lower high density lipoprotein (HDL) cholesterol, 17 hypercholesterolemic patients were treated with either a standard dose, 1 g/day (4 tablets), or a low dose, 250 mg/day (1 tablet), of probucol for a 6-month period. Effects of therapy on lipoprotein levels and on susceptibility of LDL to in vitro oxidation were measured at frequent intervals. Probucol levels in plasma LDL rose less rapidly in the 1-tablet group but were nearly 50% of levels in the 4-tablet group after 6 months. HDL cholesterol and apolipoprotein A-1 decreased 17.6% and 27.9%, respectively, in the 1-tablet group compared with 28.0% and 38.3%, respectively, in the 4-tablet group (p=0.07 and p=0.06). In the 4-tablet group, LDL was protected from copper and endothelial cell-mediated oxidation after 2 months of therapy. In the 1-tablet group, equal degrees of protection occurred, but only after 6 months of therapy. In the whole study group, the decrease in LDL susceptibility to copper or endothelial cell-mediated oxidative modification was correlated with the content of probucol in LDL (r=0.73, r=0.65, p<0.005). Additionally, the decrease in HDL cholesterol level was correlated with the increase in protection to LDL from oxidative modification (r=0.67 for copper, r=0.58 for endothelial cells, p<0.05 for both) and also with the content of probucol in LDL (r=0.6, p=0.01). In conclusion, a low dose of probucol provides impressive protection to LDL against in vitro oxidation and modification, with less marked HDL cholesterol lowering. However, these effects are not completely dissociated from each other, and in fact, the extent of HDL cholesterol lowering was correlated with the LDL probucol content and the resulting antioxidant protection. (Arteriosclerosis and Thrombosis 1992;12:318-324).
AB - To determine whether probucol's ability to confer antioxidant protection to low density lipoprotein (LDL) could be dissociated from its ability to lower high density lipoprotein (HDL) cholesterol, 17 hypercholesterolemic patients were treated with either a standard dose, 1 g/day (4 tablets), or a low dose, 250 mg/day (1 tablet), of probucol for a 6-month period. Effects of therapy on lipoprotein levels and on susceptibility of LDL to in vitro oxidation were measured at frequent intervals. Probucol levels in plasma LDL rose less rapidly in the 1-tablet group but were nearly 50% of levels in the 4-tablet group after 6 months. HDL cholesterol and apolipoprotein A-1 decreased 17.6% and 27.9%, respectively, in the 1-tablet group compared with 28.0% and 38.3%, respectively, in the 4-tablet group (p=0.07 and p=0.06). In the 4-tablet group, LDL was protected from copper and endothelial cell-mediated oxidation after 2 months of therapy. In the 1-tablet group, equal degrees of protection occurred, but only after 6 months of therapy. In the whole study group, the decrease in LDL susceptibility to copper or endothelial cell-mediated oxidative modification was correlated with the content of probucol in LDL (r=0.73, r=0.65, p<0.005). Additionally, the decrease in HDL cholesterol level was correlated with the increase in protection to LDL from oxidative modification (r=0.67 for copper, r=0.58 for endothelial cells, p<0.05 for both) and also with the content of probucol in LDL (r=0.6, p=0.01). In conclusion, a low dose of probucol provides impressive protection to LDL against in vitro oxidation and modification, with less marked HDL cholesterol lowering. However, these effects are not completely dissociated from each other, and in fact, the extent of HDL cholesterol lowering was correlated with the LDL probucol content and the resulting antioxidant protection. (Arteriosclerosis and Thrombosis 1992;12:318-324).
KW - Antioxidants
KW - High density lipoprotein cholesterol
KW - Lipid peroxidation
KW - Macrophage degradation
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U2 - 10.1161/01.ATV.12.3.318
DO - 10.1161/01.ATV.12.3.318
M3 - Article
C2 - 1547191
AN - SCOPUS:0026586675
SN - 1079-5642
VL - 12
SP - 318
EP - 324
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 3
ER -