Abstract
The effect of trapidil derivative AR12456 on intracellular cholesterol metabolism was investigated in human hepatoma cell line HepG2. AR12456 enhanced the uptake and degradation of125I-LDL in a dose-dependent manner. The drug inhibited cholesterol synthesis and esterification without affecting cellular cholesterol content and bile acid synthesis; cholesterol efflux was slightly increased. These results show that the inhibition of cholesterol synthesis together with the enhanced expression of LDL receptors may partially explain the hypocholesterolemic activity of compound AR12456.
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References
Consensus conference. (1985) Lowering blood cholesterol to prevent heart disease. JAMA253,2080–2086.
Brown, M.S. and J.L. Goldstein (1986) A receptor-mediated pathway for cholesterol homeostasis. Science232,34–47.
Giessler, C.H., A. Fahr, V.V. Tertov et al. (1987) Trapidil derivative as potential antiatherosclerotic drugs. Arzneim-Forsch/Drug Res37,538–541.
Beitz, J., A. Riedel, A. Beitz, C.H. Giessler, A. Kittel, and H.-J. Mest (1991) The trapidil derivative AR12456 protects against serum hyperlipidemia in guinea pigs. J. Lipid Med.3,177–186.
Corsini, A., J. Beitz, A. Granata, R. Fumagalli, H.-J. Mest, and R. Paoletti (1989) Trapidil derivatives and low density lipoprotein metabolism by human skin fibroblasts and by human hepatoma cell line HEP G2. Pharm. Res.21,521–531.
Dashti, N., G. Wolfbauer, and P. Alaupovic (1985) Binding and degradation of human high-density lipoproteins by human hepatoma cell line HepG2. Biochim. Biophys. Acta833,100–110.
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Corsini, A., Grignaffini, P., Beitz, J. et al. Effect of trapidil derivative AR 12456 on intracellular cholesterol homeostasis in human hepatoma cell line Hep G2. Cytotechnology 11 (Suppl 1), S15–S17 (1993). https://doi.org/10.1007/BF00746043
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DOI: https://doi.org/10.1007/BF00746043