Probucole

Probucol. Probucol is an antioxidant that is effective in lowering LDL cholesterol. Whereas probucol was known to lower cholesterol after relatively simple clinical trials (160), its mechanism of action as an antioxidant in the treatment of atherosclerosis is quite novel. Probucol has been shown to have the abiUty to produce regression of atherosclerotic lesions in animal models (161). Probucol therefore represents a novel class of pharmaceutical agent for the treatment of atherosclerosis. This effect occurs mechanistically, in part, by preventing oxidation of LDL, a necessary step in foam cell formation. This antioxidant activity has been shown in laboratory experiments and its activity in lowering LDL cholesterol in human studies is well documented (162). 

Alprenolol HCl Bromelain Ciprofibrate Clortermine HCl Desonide Fenofibrate Flucloronide Flunisolide Fluocinonide Flurandrenolide Glucagon Gramicidin Hetacillin potassium I proniazid Kebuzone Methyltestosterone Niaprazine Probucol Relaxin Somatotropin Triamcinolone acetonide Acetonitrile... 

FRUEBis J, GONZALEZ v, siLVESTRE M and PALiNSKi w (1997) Effect of probucol treatment on gene expression of VCAM-1, MCP-1, and M-CSF in the aortic wall of LDL receptor-deficient rabbits during early sihsro genss.is, Arteriosclerosis, Thrombosis and Vascular Biology 17, 1289-302. 

In the case of a-tocopherol and probucol it is possible to demonstrate synergy between these antioxidants and the water-soluble antioxidant ascorbate in both model... 

Gotoh, N., Shimizu. K., Komuro, E., Tsuchiya, J., Noguchi, N. and Niki, E. (1992). Antioxidant activities of probucol against lipid peroxidations. Biochem. Biophys. Acta 1128, 147-154. 

Kalyanaraman, B., Darley-Usmar, V.M., Wood, J., Joseph, J. and Parathasarathy, S. (1992). Synergistic interaction between the probucol phenoxyl radical and ascorbic acid in inhibiting the oxidation of LDL. J. Biol. Chem. 267, 6789—6795. 

Carew, T.E., Schwenke, D.C. and Steinberg, O. (1987). Antiatherogenic effect of probucol unrelated to its hyper-cholesterolaemic effect evidence that antioxidants in vim can selectively inhibit low density lipoprotein degradation in macroph -rich fatty streaks slowing the progression of atherosclerosis in the WHHL rabbit. Proc. Natl Acad. Sci. USA 84, 7725-7729. 

Kita, T., Nagano, X., Yokode, M., Ishii, K., Kume, N., Ooshima, A., Yoshida, H. and Kawai, C. (1987). Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidaemic rabbits an animal model for hyper-cholesterolaemic. Proc. Natl Acad. Sci. USA 84, 5928-5931. 

Probucol treatment slows progression of atheroma In the Watanabe rabbit... 

Parthasarathy, S., Young, S.G., Witztum, J.L., Pittman, R.C. and Steinberg, D. (1986). Probucol inhibits oxidative modification of low density lipoprotein. J. Clin. Invest. 7, 641-644. 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

The phenothiazines, chlorpromazine and promethazine, have been described as inhibitors of CCU-induced lipid peroxidation at relatively high concentrations in rat liver microsomes (Slater, 1968). Structural modifications of chlorpromazine were undertaken to try to increase antioxidant activity and maintain molecular lipophilicity. The 2-N-N-dimethyl ethanamine methanesulphonate-substituted phenothiazine (3) was found to be a potent inhibitor of iron-dependent lipid peroxidation. It was also found to block Cu -catalysed oxidation of LDL more effectively than probucol and to protect primary cultures of rat hippocampal neurons against hydrogen peroxide-induced toxicity in vitro (Yu et al., 1992). 

Nafenopin Pimetine Probucol Tibric Acid Treloxinate... 

One of the first pharmacogenomic studies investigating lipid-lowering drags was published by Nestrack et al. in 1987 [29], describing that carriers of at least one apo E4 allele who received probucol showed the greatest cholesterol reduction in comparison to those without an apo E4 allele. These data were confirmed in a second study by Eto et al. [30]. 

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