Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Probucol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMedDate not supplied

The effect of probucol and cholestyramine combination therapy in severe familial hypercholesterolaemia.

The relative effects of cholestyramine and probucol, alone and in combination, on serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and the ratio of TC to HDL-C (T/HDL-C) have been studied in a group of 10 subjects with severe familial hypercholesterolaemia. The combination of cholestyramine plus probucol was more potent than either agent alone in reducing TC. The use of probucol either alone or in combination reduced the HDL-C concentrations, but the ratio of T/HDL-C was not consistently affected. The effect of the combination therapy did not diminish after periods of at least 6 months and in some cases led to partial regression of long-standing xanthomata. The combination of probucol with cholestyramine did not give rise to additional side effects and it is considered to be a valuable addition to the regimens available for the treatment of severe familial hypercholesterolaemia.

Cholesterol↗
PubMed1985

Double-blind, placebo-controlled, cross-over trial of probucol in heterozygous familial hypercholesterolaemia.

Ten patients with heterozygous familial hypercholesterolaemia (FH) were given probucol 500 mg b.d. or placebo for 3 months in a randomised order in a double-blind cross-over trial. There was a 14% decrease in serum cholesterol concentration due to a reduction in both low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol. The subfraction of HDL most affected was HDL2. Reductions in serum LDL cholesterol concentration exceeding 20% were obtained in 3 (30%) of the patients. The magnitude of the change in LDL cholesterol concentration was related to the level of serum HDL2 cholesterol without therapy and to the magnitude of its decrease on probucol. Intravenous intralipid tolerance was unaffected by probucol administration. Serum apolipoprotein B concentration decreased less with probucol than did that of serum LDL cholesterol.

Adolescent↗
PubMed1990

Effects of probucol on plasma lipids and lipoproteins in familial hypercholesterolemic patients with and without apolipoprotein E4.

It has been reported that total cholesterol (Chol) response to probucol is greater in familial hypercholesterolemic (FH) patients with apo E4 than in those without apo E4. We further examined the effect of probucol on plasma triglyceride (TG) and lipoprotein-Chol levels as well as total Chol levels in heterozygous FH patients with apo E4 (n = 14 for apo E4/3, n = 1 for apo E4/4) and without apo E4 (n = 31 for apo E3/3). Probucol was administered in a dosage of 500 mg twice daily for 3 months. The reduction in total Chol levels was significantly greater in FH patients with apo E4 (-90 mg/dl, -27.5%) than in those without apo E4 (-41 mg/dl, -13.7%). The reduction in low density lipoprotein (LDL)-Chol levels was also significantly greater in FH patients with apo E4 (-73 mg/dl vs. -34 mg/dl). There was a significant difference in the change in TG and very low density lipoprotein (VLDL)-Chol levels with treatment between the FH patients with apo E4 (-37 and -8 mg/dl, respectively) and without apo E4 (+8 and +2 mg/dl, respectively). However, there was no significant difference in the reduction in HDL-Chol levels between the 2 groups (-9 mg/dl vs. -9 mg/dl). It is concluded that FH patients with apo E4 showed the greater reduction in plasma TG levels as well as total Chol levels with probucol treatment than those without apo E4, and that the greater reduction in total Chol levels in them, as reported previously, was mainly due to the greater reduction in LDL-Chol levels and slightly due to that in VLDL-Chol levels.

Apolipoprotein E4↗
PubMed1990

Effect of probucol treatment on the susceptibility of low density lipoprotein isolated from hypercholesterolemic patients to become oxidatively modified in vitro.

Lipid accumulation in monocyte-originated macrophages in the subendothelial space is an important characteristic of atherosclerotic lesions. Several lines of evidence have indicated that this accumulation occurs as a result of lipid peroxidation. In the present study the ability of probucol to prevent oxidation of low density lipoprotein (LDL) was investigated in 20 hypercholesterolemic individuals taking part in the Probucol Quantitative Regression Swedish Trial (PQRST). The effect of Cu2(+)-induced oxidation of LDL on degradation by macrophages, binding to LDL receptors on fibroblasts and LDL TBARS content was analysed. With LDL isolated from patients on diet alone oxidation led to a 44.3% decreased binding to fibroblasts (P less than 0.001), a ninefold increased uptake in macrophages (P less than 0.001) and a twentyfold increase in TBARS content (P less than 0.001) as compared to native LDL. These values were essentially the same during treatment with cholestyramine alone. However, during treatment with probucol plus cholestyramine exposure of LDL to Cu2+ resulted in an increase in TBARS which was less than 50% (P less than 0.02) of that observed during the other two treatment periods. Furthermore, probucol treatment abolished more than 70% of the decrease in B,E receptor binding to fibroblasts (P less than 0.05) and more than 90% of the increased degradation by macrophages (P less than 0.001) of Cu2+ oxidatively modified LDL.

Aged↗
PubMed1991

Inhibition of IL-1 beta expression in THP-1 cells by probucol and tocopherol.

The cytokine interleukin-1, IL-1, likely plays an important role in the early stages of atherogenesis. The possible action of probucol and tocopherol on the expression and secretion of IL-1 beta was investigated using the human monocytic leukemia cell line, THP-1. Both probucol and D-alpha-tocopherol inhibit the phorbol ester-induced release of IL-1 beta without altering differentiation. Analysis of IL-1 beta mRNA levels revealed that probucol and tocopherol had an inhibitory effect on the activation of expression of the IL-1 beta gene. The data suggest that the beneficial effects of probucol may be related to inhibition of IL-1 at an early phase of atherosclerotic plaque formation.

Cell Differentiation↗
PubMed1992

Probucol reduces plasma and aortic wall oxysterol levels in cholesterol fed rabbits independently of its plasma cholesterol lowering effect.

To understand further the antiatherogenic mechanism of probucol, the antioxidant effect of this agent was studied on specific cholesterol oxidation products in plasma and aortic wall in equally hypercholesterolemic New Zealand white rabbits. In order to maintain equal plasma total cholesterol levels, five control rabbits (C group) received a 1% followed by a 0.5% cholesterol enriched diet, while the probucol treated rabbits (C+P group) received a graded increase in the cholesterol supplemented diet from 1% to 3%; probucol supplementation was constant at 1%. After 9 weeks of feeding, the plasma oxysterols, cholest-5-ene-3 beta,7 alpha-diol, cholest-5-ene-3 beta,7 beta-diol, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol and 5 alpha-cholestane-3 beta,5,6 beta-triol significantly increased over baseline levels in both experimental groups. However, the increase in all these products in plasma was 20-60% less in the C+P group than the C group (P < 0.05). Furthermore, the C+P aortic wall cholesterol oxide concentrations were 50-90% less than the C group (P < 0.05). The oxysterol pattern of the aortic wall was similar to plasma. Additionally, the aortic wall cholesterol content in the C+P group was 50% less than the C group (P < 0.05). The plasma cholesterol levels were not significantly different at any time point during the study and the cholesterol oxide content in the diets was the same. These results are consistent with the contention that the antioxidant properties of probucol serve as the basis for its antiatherogenic effects in vivo.

Animals↗
PubMed1992

Probucol protects lipoprotein (a) against oxidative modification.

Probucol, which decreases cholesterol levels and has antioxidant properties, was administered orally to patients with familial combined hyperlipidemia and high plasma lipoprotein(a) [Lp(a)] levels. The drug had no effect on Lp(a) concentrations after 4 weeks, but was found to be distributed in both Lp(a) and low-density lipoprotein (LDL). Before treatment, in each case LDL and Lp(a) isolated from the same individual were readily oxidized by copper, resulting in increased electrophoretic mobility and enhanced uptake and degradation by macrophages of both lipoproteins. After probucol treatment, both lipoproteins acquired resistance to in vitro oxidation by copper. Furthermore, probucol prevented their enhanced uptake and degradation by the macrophages. It is surmised that oxidized Lp(a) may carry an atherogenic potential that could be opposed by probucol administration.

Adult↗
PubMed1993

Probucol as an antioxidant and antiatherogenic drug.

Recently, interest has increased in the hypothesis that low-density lipoprotein (LDL) modified by oxidation may lead to the initiation and to the development of atherosclerosis. In vitro studies of cellular interactions with LDL have revealed that various cells, including endothelial cells and smooth muscle cells, can oxidize LDL. The biochemical changes in LDL may further enhance its atherogenic potential. In addition to these in vitro studies, there is in vivo evidence for oxidized LDL in atherosclerotic lesions and for circulating antibodies against oxidized LDL. Probucol, 4,4'-(isopropylidenedithio)bis(2,6-di-tert-butylphenol), is a widely used cholesterol-lowering drug. Recently, there has been accumulating evidence for other mechanisms of probucol's antiatherogenic effects apart from cholesterol-lowering action. Attention has especially focused on probucol's antioxidant action in the mechanism of antiatherogenesis. In the present article, we will summarize the antiatherogenic and antioxidant actions of probucol.

Animals↗
PubMed1991

Ultraviolet-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cells. III. The protective effect of antioxidants (probucol, catechin, vitamin E) against the cytotoxicity of oxidized LDL occurs in two different ways.

Comparison of the protective effect of three antioxidants (from three different chemical classes) against cell injury due to LDL oxidation, allowed us to clearly discriminate between two different lines of defence. The ultraviolet-induced lipid peroxidation of LDL was strongly inhibited by 10 mumol/l catechin and 25 mumol/l probucol, but only poorly by 100 mumol/l vitamin E. The ultraviolet-treated LDL protected by catechin or probucol (i.e. LDL irradiated by ultraviolet in the presence of effective concentrations of antioxidants inhibiting the lipid peroxidation) were much less 'cytotoxic' than unprotected ultraviolet-treated LDL. In contrast, LDL treated by ultraviolet in the presence of 100 mumol/l vitamin E were 'cytotoxic' similarly to unprotected LDL. The level of 'cytotoxicity' of LDL treated by ultraviolet in the presence of antioxidants (protected ultraviolet-treated LDL) was well correlated with their content in lipid peroxidation markers. Therefore these markers can be useful for predicting the 'cytotoxicity' of oxidized LDL and subsequently the protective effect of the tested antioxidants. The 'cytotoxicity' of unprotected ultraviolet-treated LDL (i.e. LDL irradiated by ultraviolet in the absence of exogenous antioxidant) can be effectively blocked by preincubation of the cells with antioxidants. Catechin (10 mumol/l) and vitamin E (100 mumol/l) are very effective cytoprotective agents, whereas probucol (up to 50 mumol/l) was completely ineffective under these experimental conditions. The cytoprotective effect of vitamin E was associated to a complete inhibition of the cellular TBARS formation induced by ultraviolet-treated LDL, whereas the cytoprotective effect of catechin was relatively independent on the TBARS inhibition. All these results showed that: (1) probucol (25 mumol/l) is very effective to prevent lipid peroxidation of LDL and their subsequent 'cytotoxicity', but it cannot protect cells against the 'cytotoxicity' of previously oxidized LDL; (2) vitamin E (100 mumol/l) prevents poorly the ultraviolet-induced lipid peroxidation of LDL, but is able to block simultaneously the cellular oxidative stress and the 'cytotoxicity' induced by previously oxidized LDL; and (3) catechin (10 mumol/l) exhibited two types of protective effects: it inhibits the lipid peroxidation of LDL (and their subsequent 'cytotoxicity') and very effectively protects the cells against 'toxicity' of previously oxidized LDL (with only little inhibition of the cellular oxidative stress).(ABSTRACT TRUNCATED AT 400 WORDS)

Antioxidants↗
PubMed2004

Probucol and ticlopidine: effect on platelet and monocyte activation markers in hyperlipidemic patients with and without type 2 diabetes.

We investigated the effects of probucol and ticlopidine on circulating levels of platelet activation markers, microparticles, soluble selectins, and malondialdehyde-low density lipoprotein (MDA-LDL) in hyperlipidemic patients with or without type 2 diabetes. There were significant differences in the levels of CD62P, PAC-1, annexin V, PDMP, MDMP, sP-selectin, sE-selectin and MDA-LDL between the hyperlipidemic patients and the controls. In particular, these markers were significantly increased in hyperlipidemic patients who had type 2 diabetes. In the hyperlipidemic patients with diabetes, MDA-LDL was decreased by both monotherapy with probucol and combination therapy (probucol and ticlopidine). In these patients, CD62P, PAC-1, annexin V, MDMP, PDMP, sP-selectin, and sE-selectin were also significantly decreased after treatment. The decreases of CD62P, PAC-1, annexin V, PDMP and sP-selectin were greater combination therapy than with monotherapy. These findings suggest that administration of probucol and ticlopidine to hyperlipidemic patients with type 2 diabetes may help to prevent the development of cardiovascular complications caused by modified LDL, selectins, or activated platelets and monocytes.

Aged↗
PubMed2006

Combined effect of probucol and insulin on renal damage in diabetic rats fed a high cholesterol diet.

We investigated the effects of long-term treatment with probucol, a hypolipidemic agent with antioxidative action, insulin, or their combination on renal damage in streptozotocin-induced diabetic rats fed a high cholesterol diet. Increases in urinary albumin and lipid peroxide excretions were observed in these diabetic rats, when both urinary parameters were measured at 8 and 15 weeks after streptozotocin administration. Daily treatment with probucol, insulin, or their combination markedly suppressed the increase in the 24 h urinary albumin and lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules, fatty degeneration of glomerular endothelium, and hypertrophy of glomeruli and mesangium were observed in the kidneys of the diabetic animals, when histopathological evaluation was performed at 4, 8 and 15 weeks (glomerular and mesangial hypertrophy was observed only at 15 weeks). Combined probucol and insulin treatment was the most effective in suppressing these renal histopathological changes. These results indicate that combined treatment with probucol and insulin is useful in preventing the progression of renal damage in diabetic rats. The possible mechanisms for the preventive effect of this combined treatment will be discussed.

Albuminuria↗
PubMed1988

In vivo inhibition of foam cell development by probucol in Watanabe rabbits.

Previous studies from this laboratory have shown that oxidative modification of low-density lipoprotein (LDL) causes it to be recognized by the scavenger receptor of the macrophage. Consequently, the rate of degradation of oxidized LDL by macrophages can be 3 to 10 times that of native LDL. Antioxidants, such as probucol, are highly effective in preventing the oxidative modification of LDL. Our recent studies show that probucol treatment of LDL receptor-deficient Watanabe heritable hyperlipidemic (WHHL) rabbits selectively inhibits the degradation of LDL in fatty streak lesions (which are rich in macrophage-derived foam cells) without inhibiting degradation in nonlesioned areas (where degradation is predominantly in smooth muscle cells, which do not express the scavenger receptor). Furthermore, the rate of progression of lesions in probucol-treated animals was significantly slower than in a lovastatin-treated group maintained at equal total plasma cholesterol levels. These results strongly suggest that probucol, through an antioxidant activity not necessarily related to its ability to lower plasma cholesterol levels, can slow the progression of the foam-cell-rich fatty streak lesion of atherosclerosis.

Animals↗
PubMed1988

Prevention of atherosclerotic progression in Watanabe rabbits by probucol.

The foam cell has been recognized as a characteristic feature of xanthomas in skin and tendons, and also of atheromas. Many foam cells in these lesions share properties characteristic of the macrophages. Therefore macrophages may be the progenitor of certain foam cells that are involved in atherogenesis. Several investigators demonstrated in vitro that macrophages can ingest large amounts of certain chemically modified lipoproteins, such as acetylated low-density lipoprotein (LDL) and malondialdehyde-treated LDL, through the process of receptor-mediated endocytosis. By this process, macrophages become foam cells. But this process has not been demonstrated in vivo. Recently, oxidized LDL has been suggested to play an important role in atherogenesis by facilitating the accumulation of lipids in macrophages in vitro. Probucol, originally developed as an antioxidant, prevents this oxidative modification of LDL in vitro. Moreover, there are some clinical reports that probucol induces regression of cutaneous and tendon xanthomas in patients with homozygous familial hypercholesterolemia. A question was posed whether in vivo probucol could prevent the progression of atherosclerosis in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. At age 2 months, 8 WHHL rabbits were classified into 2 groups: group A rabbits were controls and group B rabbits were treated with 1% probucol. After 6 months of treatment, average plasma concentrations of cholesterol were 704 +/- 121 mg/dl in group A and 584 +/- 61 mg/dl in group B. The percentage of surface area of total thoracic aorta with visible plaques in group A vs group B was 54.2 +/- 18.8% vs 7.0 +/- 6.3%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol Quantitative Regression Swedish Trial (PQRST): a status report.

The Probucol Quantitative Regression Swedish Trial is being performed to investigate the effects of probucol on atherosclerosis in the femoral artery. Probucol is combined with cholestyramine and dietary management in hypercholesterolemic patients, and the effects of atheroma developing in the femoral artery will be followed by a quantitative angiographic technique. A randomly selected control group is also being managed by dietary therapy and cholestyramine, but receives placebo instead of probucol. The treatment time in this double-blind trial is 3 years, and femoral angiography is performed yearly. Detailed lipoprotein and apolipoprotein analysis are performed at monthly intervals. The basic study design is described here, and some results from the open prerandomization phase of the study are presented.

Arteriosclerosis↗
PubMed1988

Probucol enhances cholesterol efflux from cultured human skin fibroblasts.

To explore whether the reported xanthoma-reducing effects of probucol are related to tissue-specific mechanisms of the drug, the influence of probucol on cholesterol efflux from cultured human skin fibroblasts was investigated. Incubation of cells with probucol led to a 2-fold enhancement of high-density lipoprotein-mediated cholesterol efflux. This result raises the possibility that probucol may reduce cholesterol accumulation in tissues through a cholesterol-mobilizing action.

Cells, Cultured↗
PubMed1988

Changes in high-density lipoprotein subfraction distribution and increased cholesteryl ester transfer after probucol.

The effects of probucol (500 mg twice daily) on high-density lipoprotein (HDL) subfractions and cholesteryl ester transfer from HDL to lower density lipoproteins were tested in a series of patients with Type II hypercholesterolemia. In this placebo-controlled crossover trial, patients received probucol or placebo for 8 weeks, then switched to the other agent for another 8 weeks. Probucol significantly lowered total, low-density lipoprotein and HDL cholesterol levels. HDL subfractions, separated by rate zonal ultracentrifugation, showed a dramatic reduction in HDL2, whereas changes in HDL3 were not significant. Both subfractions eluted at a characteristically lower volume, indicating a reduced flotation rate. These findings were confirmed by gradient gel electrophoretic separation, which showed a typical reduction or disappearance of HDL2b particles and the prevalence of particles in the HDL3a-HDL3b electrophoretic range in almost all patients. After treatment, cholesteryl ester transfer from HDL to lower density lipoproteins was significantly increased in all patients. These data suggest that probucol may accelerate HDL particle conversion, leading to improvement in reverse cholesterol transport from the periphery to the liver, through HDL and very low density lipoprotein.

Carrier Proteins↗
PubMed2002

Comparison of the effects of alpha-tocopherol, ubiquinone-10 and probucol at therapeutic doses on atherosclerosis in WHHL rabbits.

Oxidative modification of lipoproteins may trigger and maintain atherogenesis. We compared the effects of different antioxidants (alpha-tocopherol, probucol, ubiquinone-10) at doses similar to those used in humans in Watanabe Heritable Hyperlipidemic (WHHL) rabbits for 12 months. Aortic lesions were analyzed for their extent and cellular composition of lesions, mean thickness of fibrous caps and density of smooth muscle cells therein, content of antioxidants, non-oxidized and oxidized lipids. Compared to controls, probucol significantly lowered the extent and macrophage content of lesions and increased the existence and smooth muscle cell density of fibrous caps. alpha-Tocopherol supplementation increased the aortic content of vitamin E, but had no decreasing effect on either the accumulation of macrophage-specific antigen in the aorta or lesion size. Nevertheless, both probucol and alpha-tocopherol significantly decreased in vitro LDL oxidizability, measured under typically strong oxidative conditions. Ubiquinone-10 supplement increased lesion size and the fraction of lesions containing fibrous caps; however, LDL oxidizability remained unaffected by ubiquinone-10 treatment. None of the antioxidants tested lowered oxidized lipids within aortic tissue; however, long-term treatment with probucol provided the most effective anti-atherosclerotic effect, while alpha-tocopherol may be pro-atherogenic and ubiquinone-10 exerts ambivalent effects. Our data suggest that (i) widely used oxidation measures, such as ex-vivo LDL oxidizability, do not reflect the degree of atherosclerosis; and (ii) long-term beneficial effects of relatively low doses of antioxidants may be outweighed by high levels of plasma cholesterol in WHHL rabbits.

Animals↗
PubMed1998

Dual effects of the antioxidant agents probucol and carvedilol on proliferative and fatty lesions in hypercholesterolemic rabbits.

The in vivo direct antiatherogenic activity of the antioxidant probucol (200 mg/kg per day) or the beta-blocker with antioxidant properties carvedilol (10 and 20 mg/kg per day) was tested in the same animal in two different types of atherosclerotic lesion (proliferative and fatty lesions) induced in cholesterol-fed rabbits (1%). Drugs were given daily mixed with standard diet for 8 weeks; body weight and plasma lipid profile were not different among groups throughout the study. Aortic fatty lesions were induced by cholesterol feeding (n = 25 in each group) and their extent expressed as % of aorta inner surface covered by plaques was significantly reduced by both drugs (28.2+/-9.6%, P <0.05, 19.9+/-6.2%, P <0.01 for low- and high-dose carvedilol, respectively; 22.3+/-7.6%, P <0.01 for probucol, versus 41.6+/-10.7% in control rabbits). Proliferative lesions were obtained by positioning a hollow silastic collar around one carotid artery 6 weeks after dietary and drug treatments started (n = 5 in each group). The neointimal formation, mostly composed by myocytes, was determined by measuring cross-sectional thickness ratio of intimal (I) and medial (M) tissue of fixed arteries. In untreated animals, collared arteries resulted in a significant neointimal cell accumulation compared to the sham (1.10+/-0.14 versus 0.02+/-0.01) without change in medial thickness. I/M ratio was reduced by about 50% in animals treated with probucol (0.51+/-0.1) and carvedilol (0.66+/-0.21 and 0.52+/-0.1 in the low- and high-dose group, respectively). Total plasma TBARS were more than 50% lower in both probucol- and high-dose carvedilol-treated rabbits. Results show that pharmacological pretreatment with antioxidants directly inhibits early atherogenic processes, representing a potentially useful approach in the prevention of atherosclerosis.

Adrenergic beta-Antagonists↗