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Chemical Compound Review

Lurselle     4-[2-(4-hydroxy-3,5-ditert- butyl...

Synonyms: probucol, Lorelco, Panavir, Biphenabid, Superlipid, ...
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Disease relevance of Lorelco


Psychiatry related information on Lorelco

  • Approximately 40% of the mice in the probucol-treated group and 10% of the animals in the combination therapy group developed skin lesions [6].
  • A recent clinical study using Probucol in elderly AD subjects revealed a concomitant stabilisation of cognitive symptoms and significant increases in apoE levels in the cerebral spinal fluid in these patients [7].

High impact information on Lorelco


Chemical compound and disease context of Lorelco


Biological context of Lorelco

  • Probucol and its sulphur-containing metabolite, but not a sulphur-free phenolic analogue, protected via cell-specific effects on inhibiting macrophage accumulation, stimulating reendothelialization, and inhibiting vascular smooth muscle cell proliferation [9].
  • Bisphenol and probucol treatment both enhanced the resistance of circulating LDL to peroxyl radical-induced lipid peroxidation; this was due to bisphenol, not probucol [15].
  • From these findings, we conclude that probucol, a lipid-soluble antioxidant, preserves EDRF action in cholesterol-fed rabbits in association with limiting vascular oxidative stress and superoxide generation [16].
  • Its biological availability was much greater: almost comparable concentrations in total plasma were achieved by feeding 1% probucol (wt/wt) and 0.05% analogue (wt/wt) [3].
  • The fact that probucol prevented the hemodynamic abnormalities as well as the increased TX production is consistent with the hypothesis that LDL oxidized in vivo initiates events leading to TX mediated vasoconstriction [17].

Anatomical context of Lorelco

  • Most importantly, samples of LDL isolated from plasma of hypercholesterolemic patients under treatment with conventional dosages of probucol were shown to be highly resistant to oxidative modification either by incubation with endothelial cells or by cupric ion in the absence of cells [18].
  • Lesions in the probucol-treated animals appeared less mature, and increased accumulation of lipid was observed in smooth muscle cells [19].
  • However, pretreatment of LDL with probucol or pretreatment of the cocultures with probucol, beta-carotene, or alpha-tocopherol before the addition of LDL prevented the LDL-induced monocyte transmigration [20].
  • Histologically, lesions in probucol-treated mice contained increased fibrous materials and cells other than foam cells, and were commonly associated with focal inflammation and aneurysmal dilatation [21].
  • LDL and aortas from rabbits fed probucol contained bisphenol at concentrations comparable to those in bisphenol-treated animals [15].

Associations of Lorelco with other chemical compounds


Gene context of Lorelco


Analytical, diagnostic and therapeutic context of Lorelco


  1. Polymorphic ventricular tachycardia (Torsade de Pointes) associated with the use of probucol. Gohn, D.C., Simmons, T.W. N. Engl. J. Med. (1992) [Pubmed]
  2. Probucol (Lorelco) in treatment of hyperlipemia. Murphy, B.F. JAMA (1977) [Pubmed]
  3. A comparison of the antiatherogenic effects of probucol and of a structural analogue of probucol in low density lipoprotein receptor-deficient rabbits. Fruebis, J., Steinberg, D., Dresel, H.A., Carew, T.E. J. Clin. Invest. (1994) [Pubmed]
  4. Proteinuria in passive Heymann nephritis is associated with lipid peroxidation and formation of adducts on type IV collagen. Neale, T.J., Ojha, P.P., Exner, M., Poczewski, H., Rüger, B., Witztum, J.L., Davis, P., Kerjaschki, D. J. Clin. Invest. (1994) [Pubmed]
  5. Ischemic acute renal failure and antioxidant therapy in the rat. The relation between glomerular and tubular dysfunction. Bird, J.E., Milhoan, K., Wilson, C.B., Young, S.G., Mundy, C.A., Parthasarathy, S., Blantz, R.C. J. Clin. Invest. (1988) [Pubmed]
  6. Dietary phytosterols reduce probucol-induced atherogenesis in apo E-KO mice. Moghadasian, M.H. Atherosclerosis (2006) [Pubmed]
  7. The cholesterol-lowering drug probucol increases apolipoprotein E production in the hippocampus of aged rats: implications for Alzheimer's disease. Champagne, D., Pearson, D., Dea, D., Rochford, J., Poirier, J. Neuroscience (2003) [Pubmed]
  8. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. Multivitamins and Probucol Study Group. Tardif, J.C., Cöté, G., Lespérance, J., Bourassa, M., Lambert, J., Doucet, S., Bilodeau, L., Nattel, S., de Guise, P. N. Engl. J. Med. (1997) [Pubmed]
  9. Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging. Wu, B.J., Kathir, K., Witting, P.K., Beck, K., Choy, K., Li, C., Croft, K.D., Mori, T.A., Tanous, D., Adams, M.R., Lau, A.K., Stocker, R. J. Exp. Med. (2006) [Pubmed]
  10. Abnormally high thromboxane biosynthesis in homozygous homocystinuria. Evidence for platelet involvement and probucol-sensitive mechanism. Di Minno, G., Davì, G., Margaglione, M., Cirillo, F., Grandone, E., Ciabattoni, G., Catalano, I., Strisciuglio, P., Andria, G., Patrono, C. J. Clin. Invest. (1993) [Pubmed]
  11. Propranolol for probucol-induced QT prolongation with polymorphic ventricular tachycardia. Kajinami, K., Takekoshi, N., Mabuchi, H. Lancet (1993) [Pubmed]
  12. Colestipol and probucol: treatment of primary and familial hypercholesterolemia and amelioration of atherosclerosis. Glueck, C.J. Ann. Intern. Med. (1982) [Pubmed]
  13. Probucol with colestipol in the treatment of hypercholesterolemia. Dujovne, C.A., Krehbiel, P., Decoursey, S., Jackson, B., Chernoff, S.B., Pitterman, A., Garty, M. Ann. Intern. Med. (1984) [Pubmed]
  14. Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose. Yasunari, K., Kohno, M., Kano, H., Yokokawa, K., Minami, M., Yoshikawa, J. Circulation (1999) [Pubmed]
  15. Dissociation of atherogenesis from aortic accumulation of lipid hydro(pero)xides in Watanabe heritable hyperlipidemic rabbits. Witting, P., Pettersson, K., Ostlund-Lindqvist, A.M., Westerlund, C., Wâgberg, M., Stocker, R. J. Clin. Invest. (1999) [Pubmed]
  16. Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation. Keaney, J.F., Xu, A., Cunningham, D., Jackson, T., Frei, B., Vita, J.A. J. Clin. Invest. (1995) [Pubmed]
  17. Renal vasoconstriction caused by short-term cholesterol feeding is corrected by thromboxane antagonist or probucol. Kaplan, R., Aynedjian, H.S., Schlondorff, D., Bank, N. J. Clin. Invest. (1990) [Pubmed]
  18. Probucol inhibits oxidative modification of low density lipoprotein. Parthasarathy, S., Young, S.G., Witztum, J.L., Pittman, R.C., Steinberg, D. J. Clin. Invest. (1986) [Pubmed]
  19. Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol. I. Is the extent of atherosclerosis related to resistance of LDL to oxidation? Sasahara, M., Raines, E.W., Chait, A., Carew, T.E., Steinberg, D., Wahl, P.W., Ross, R. J. Clin. Invest. (1994) [Pubmed]
  20. Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. Navab, M., Imes, S.S., Hama, S.Y., Hough, G.P., Ross, L.A., Bork, R.W., Valente, A.J., Berliner, J.A., Drinkwater, D.C., Laks, H. J. Clin. Invest. (1991) [Pubmed]
  21. Paradoxical enhancement of atherosclerosis by probucol treatment in apolipoprotein E-deficient mice. Zhang, S.H., Reddick, R.L., Avdievich, E., Surles, L.K., Jones, R.G., Reynolds, J.B., Quarfordt, S.H., Maeda, N. J. Clin. Invest. (1997) [Pubmed]
  22. Restenosis: a challenge for pharmacology. Bult, H. Trends Pharmacol. Sci. (2000) [Pubmed]
  23. Probucol inactivates ABCA1 in the plasma membrane with respect to its mediation of apolipoprotein binding and high density lipoprotein assembly and to its proteolytic degradation. Wu, C.A., Tsujita, M., Hayashi, M., Yokoyama, S. J. Biol. Chem. (2004) [Pubmed]
  24. Probucol promotes reverse cholesterol transport in heterozygous familial hypercholesterolemia. Effects on apolipoprotein AI-containing lipoprotein particles. Adlouni, A., El Messal, M., Saïle, R., Parra, H., Fruchart, J., Ghalim, N. Atherosclerosis (2000) [Pubmed]
  25. Regulation of mitochondrial transcription factor A expression by high glucose. Choi, Y.S., Lee, K.U., Pak, Y.K. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  26. Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice: possible mechanisms of action. Moghadasian, M.H., McManus, B.M., Godin, D.V., Rodrigues, B., Frohlich, J.J. Circulation (1999) [Pubmed]
  27. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. Sirtori, C.R., Franceschini, G. N. Engl. J. Med. (1997) [Pubmed]
  28. Probucol decreases neointimal formation in a swine model of coronary artery balloon injury. A possible role for antioxidants in restenosis. Schneider, J.E., Berk, B.C., Gravanis, M.B., Santoian, E.C., Cipolla, G.D., Tarazona, N., Lassegue, B., King, S.B. Circulation (1993) [Pubmed]
  29. Effects of probucol on vascular remodeling after coronary angioplasty. Multivitamins and Protocol Study Group. Côté, G., Tardif, J.C., Lespérance, J., Lambert, J., Bourassa, M., Bonan, R., Gosselin, G., Joyal, M., Tanguay, J.F., Nattel, S., Gallo, R., Crépeau, J. Circulation (1999) [Pubmed]
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