TY - JOUR
T1 - Comparison of effects of probucol versus vitamin E on ex vivo oxidation susceptibility of lipoproteins in hyperlipoproteinemia
AU - Dujovne, Carlos A.
AU - Harris, William S.
AU - Colle Gerrond, Linda L.
AU - Fan, Junyuan
AU - Muzio, Fulvio
N1 - Funding Information:
From the Lipid and Arteriosclerosis Prevention Clinic, Division of Clinical Pharmacology,D epartment of Medicine, University of Kansas Medical Center, Kansas City, Kansas.T his study was supportedi n part by a grant from Marion Merrell Dow, Kansas City, Missouri. Manuscript received August 27,1993; revised manuscript received and accepted December 17, 1993. Address for reprints: Linda L. Colle Gerrond, MD, 1348 Kansas University Hospital, 3901 Rainbow Boulevard, Kansas City, Kansas 66160-7374. Dr. Muzio was a ResearchF ellow in Clinical Pharmacology from Santa Corona Hospital, GarnagnateM ilanese, Milan, Italy.
PY - 1994/7/1
Y1 - 1994/7/1
N2 - Oxidative modification of low-density lipoprotein (LDL) cholesterol appears to contribute to atherogenesis. Probucol reduces LDL cholesterol oxidation susceptibility, but the consistency, dose, and time course are not well described. Twelve hyperlipidemic patlents were given probucol for 4 weeks at the usual dose for cholesterol reduction (1,000 mg/day), or one half (500 mg/day) or one quarter (250 mg/day) the usual dose. Lipoprotein oxidation susceptibility of apolipoprotein B-containing lipoproteins was assessed using a rapid test in which LDL cholesterol and very-low-density lipoprotein are precipitated with dextran sulfate and magnesium ions, redissolved, incubated with copper ions for 3 hours, and tested for thiobarbituric acid-reactive substances. Results are expressed as nmoles of malonyldialdehyde (MDA) generated per mg (nmol MDA/mg) non-high-density lipoprotein cholesterol. Lipoproteins from probucol-treated patients become resistant to oxidation with a predrug value of 85 ± 19, and decreasing to 3 ± 1 nmol MDA/mg after drug administration (p < 0.001). Both "half" and "full" doses were effective in lowering lipoprotein oxidation susceptibility by 95%. The "quarter" dose was less effective. Oxidation inhibition was maximized within 2 weeks, returning to baseline 4 to 6 weeks after discontinuing probucol. Four patients were subsequently crossed over to vitamin E (1,200 IU/day). Vitamin E had a milder, less predictable antioxidant effect, towering lipoprotein oxidation susceptibility by a mean of 24%. In conclusion, probucol treatment effectively and predictably reduces plasma lipoprotein susceptibility to ex vivo, copper-induced oxidation. This clinically applicable test may provide quantitation of antioxidant effects of probucol or other antioxidants and thus facilitate dose adjustments and correlation with antiatherosclerotic effects.
AB - Oxidative modification of low-density lipoprotein (LDL) cholesterol appears to contribute to atherogenesis. Probucol reduces LDL cholesterol oxidation susceptibility, but the consistency, dose, and time course are not well described. Twelve hyperlipidemic patlents were given probucol for 4 weeks at the usual dose for cholesterol reduction (1,000 mg/day), or one half (500 mg/day) or one quarter (250 mg/day) the usual dose. Lipoprotein oxidation susceptibility of apolipoprotein B-containing lipoproteins was assessed using a rapid test in which LDL cholesterol and very-low-density lipoprotein are precipitated with dextran sulfate and magnesium ions, redissolved, incubated with copper ions for 3 hours, and tested for thiobarbituric acid-reactive substances. Results are expressed as nmoles of malonyldialdehyde (MDA) generated per mg (nmol MDA/mg) non-high-density lipoprotein cholesterol. Lipoproteins from probucol-treated patients become resistant to oxidation with a predrug value of 85 ± 19, and decreasing to 3 ± 1 nmol MDA/mg after drug administration (p < 0.001). Both "half" and "full" doses were effective in lowering lipoprotein oxidation susceptibility by 95%. The "quarter" dose was less effective. Oxidation inhibition was maximized within 2 weeks, returning to baseline 4 to 6 weeks after discontinuing probucol. Four patients were subsequently crossed over to vitamin E (1,200 IU/day). Vitamin E had a milder, less predictable antioxidant effect, towering lipoprotein oxidation susceptibility by a mean of 24%. In conclusion, probucol treatment effectively and predictably reduces plasma lipoprotein susceptibility to ex vivo, copper-induced oxidation. This clinically applicable test may provide quantitation of antioxidant effects of probucol or other antioxidants and thus facilitate dose adjustments and correlation with antiatherosclerotic effects.
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U2 - 10.1016/0002-9149(94)90488-X
DO - 10.1016/0002-9149(94)90488-X
M3 - Article
C2 - 8017303
AN - SCOPUS:0028360671
SN - 0002-9149
VL - 74
SP - 38
EP - 42
JO - The American journal of cardiology
JF - The American journal of cardiology
IS - 1
ER -