Effectiveness of probucol in reducing plasma low-density lipoprotein cholesterol oxidation in hypercholesterolemia.
Oxidized low-density lipoprotein (LDL) interacts with macrophages to induce intracellular cholesterol ester accumulation and foam cell formation. Probucol is a lipid-lowering drug with a well-known antioxidant action. The thiobarbituric acid (TBA)-reacting substances were measured as an index of plasma and LDL lipid peroxidation in a group of hypercholesterolemic patients compared with a normolipidemic control group. The effect of probucol treatment on plasma and LDL lipid peroxidation in the hypercholesterolemic group was also evaluated. Twenty-five patients (10 men and 15 women) with total cholesterol levels greater than 6.5 mmol/liter were given probucol for 24 weeks. Lipid and apoprotein measurements were obtained at 0, 12 and 24 weeks. TBA-reacting substances were also measured in plasma and the LDL fraction. Twenty-five normolipidemic subjects matched for sex, age and body mass index underwent complete blood analysis for purposes of comparison at week 0. Plasma, LDL and high-density lipoprotein cholesterol, and plasma apoproteins A-I and B significantly decreased after 12 and 24 weeks of probucol treatment. Hypercholesterolemic subjects (men and women) had significantly higher TBA-reacting substances in plasma and LDL than control subjects had (p less than 0.05). The amount of TBA-reacting substances in plasma and LDL showed a very significant decrease after probucol treatment (40 and 44%, respectively, after 24 weeks; p less than 0.05). This reduction was not related to age, sex or body mass index, and was greater than the decrease in lipids. These results support a potential role for probucol as a coadjuvant drug in any lipid-lowering antiatherogenic therapy.
Unitat de Recerca de Lípids, Hospital de Sant Joan, Facultat de Medicina de Reus, Universitat de Barcelona, Spain.
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L
Masana
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MT
Bargalló
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N
Plana
A
A
LaVille
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I
Casals
R
R
Solà
D000328:Adult; D000368:Aged; D001054:Apolipoproteins A / Q000032:analysis; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D001054:Apolipoproteins A; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D011341:Probucol