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Probucol and its Mechanisms for Reducing Atherosclerosis

  • Richard L. Jackson
  • Roger L. Barnhart
  • Simon J. T. Mao
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 285)

Abstract

Probucol (1) is a marketed lipid-lowering drug used in the treatment of hypercholesterolemia, including forms of familial hypercholesterole mia. In hyperlipidemic subjects, probucol reduces total plasma cholesterol and low density lipoprotein (LDL)-cholesterol by 10 to 20% and high density lipoprotein (HDL)-cholesterol by 20 to 30% (2). The drug has little or no effect on triglyceride concentrations in hypercholesterolemic subjects, although Hattori et al. (3) reported a significant reduction in serum triglycerides with probucol treatment in patients with noninsulin-dependent diabetes mellitus. The mechanism by which probucol reduces plasma cholesterol is not known with certainty. The most convincing evidence in man is that it increases the fractional catabolic rate of LDL clearance (4,5) and enhances bile acid excretion (5,6). The fall in HDL-cholesterol with probucol treatment results from a decrease in the rate of synthesis of apo A-I and apo A-II (5,7), the major protein constituents of HDL. In addition to its lipid-lowering activity probucol is a potent antioxidant, and it is this property which prevents cell and metal ion-mediated oxidative modification of LDL (8). Mao et al. (9) synthesized a number of analogs of probucol that retained the antioxidant property but had little or no lipid-lowering activity. Even though lipid levels were unchanged, these analogs were effective in reducing atherosclerosis in modified Watanabe heritable hyperlipedemic (WHHL) rabbits, suggesting that other mechanisms besides lipid-lowering account for this antiatherosclerotic property.

Keywords

Smooth Muscle Cell Proliferation Foam Cell Formation Cholesteryl Ester Hydrolase Fractional Catabolic Rate Butyl Phenol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Richard L. Jackson
    • 1
  • Roger L. Barnhart
    • 1
  • Simon J. T. Mao
    • 1
  1. 1.Merrell Dow Research InstituteCincinnatiUSA

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