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 1,171 records · Page 65Linked to original sources
PubMed1992

Free radical-mediated postischemic injury in renal transplantation.

Oxygen free radicals are generated during reperfusion of ischemic organs. Studies employing several species of laboratory animal (rat, dog, pig, rabbit, mouse) have documented protective effects of a variety of free-radical scavengers and antioxidants when administered before or immediately preceding reperfusion of ischemic kidneys. These protective agents include superoxide dismutase, dimethylthiorea, dimethyl sulfoxide, alpha-tocopherol, glutathione, the iron chelator deferoxamine, probucol, allopurinol and oxypurinol, and the spin-trapping agent PBN. Furthermore, deficiency of antioxidants (selenium, alpha-tocopherol, or catalase) exacerbates postischemic renal injury. These findings have been applied to renal transplantation in an attempt to decrease the incidence of posttransplantation acute renal failure. This is important because acute renal failure results in morbidity, increases hospital stay and the cost of transplantation, and complicates the use of cyclosporine. In porcine and in canine kidney transplantation, superoxide dismutase and allopurinol have provided renal protection. Transplantation is complicated because there may be prolonged hypoperfusion before harvesting plus a brief period of total ischemia during harvesting, followed by a prolonged period of cold ischemia and/or reperfusion, then followed by another brief period of ischemia and reperfusion during transplantation. Injury may occur at each of these phases by different mechanisms.

Acute Kidney Injury↗
PubMed1995

Diphenylhexatriene as a fluorescent probe for monitoring low density lipoprotein peroxidation.

The use of the fluorescent probe diphenylhexatriene (DPH) for monitoring low density lipoprotein (LDL) peroxidation has been investigated. The DPH incorporation into LDL results in a high fluorescence signal which decreases with time after addition of cupric ions. A strong correlation was found between the decay of the DPH fluorescence signal and the appearance of the thiobarbituric reactive substances (TBARS). HPLC and spectrofluorometric analyses demonstrated that DPH is destroyed during the time course of the copper-induced LDL peroxidation. The decrease in DPH fluorescent signal is prevented by addition of EDTA, vitamin E and drugs which protect LDL against peroxidation such as probucol or calcium antagonists. The high fluorescence of DPH allows the use of very small quantities of LDL (less than 5 micrograms/ml LDL protein). We thus suggest that DPH could be of use for continuous monitoring of LDL autooxidation, especially for the in vitro testing of the protective effect of antioxidant compounds.

Diphenylhexatriene↗
PubMed1996

Influence of the environment in space on the biochemical characteristics of human low density lipoproteins.

The purpose of this experiment was to study the efficiency of protective substances on the effects of cosmic radiation in space on low density lipoproteins. This environment induced modifications in LDL consisting of an increase of lipid peroxidation markers (hydroperoxides, thiobarbituric acid reactive substances). In contrast, apo B was not affected by cosmic radiation as shown by the stability of the trinitrobenzenesulfonic acid reactivity and the tryptophan content. Furthermore, oxidation of LDL was partially inhibited by the addition of cysteamine or/and probucol before the spaceflight experiment. The hydroperoxide formation was almost completely inhibited by cysteamine. It was concluded that antioxidants can exert a protective effect against peroxidative stress induced by the space environment.

Cosmic Radiation↗
PubMed1997

Toxicity of polyunsaturated fatty acid esters for human monocyte-macrophages: the anomalous behaviour of cholesteryl linolenate.

We have investigated the toxicity to human monocytemacrophages, and susceptibility to oxidation, of different individual dietary fatty acids in cholesterol esters and triglycerides, added to the cell cultures as coacervates with bovine serum albumin. Toxicity was assessed using release of radioactivity from cells preloaded with tritiated adenine. Lipid oxidation was measured by gas chromatography (GC). The triglycerides showed a direct relationship between toxicity and increasing unsaturation, which in turn correlated with increasing susceptibility to oxidation. Triolein (18:1; omega-9) and trilinolein (18:2; omega-6) were non-toxic. Trilinolenin (18:3; omega-3) was toxic only after prolonged incubation. Triarachidonin (20:4; omega-6), trieicosapentaenoin (20:5; omega-3) and tridocosahexaenoin (22:6; omega-3) were profoundly and rapidly toxic. There was a similar relationship between toxicity and increasing unsaturation for most of the cholesterol esters, but cholesteryl linolenate was apparently anomalous, being non-toxic in spite of possessing three double bonds and being extensively oxidised. Probucol and DL-alpha-tocopherol conferred protection against the toxicity of cholesteryl arachidonate and triarachidonin. The oxidation in these experiments was largely independent of the presence of cells. GC indicated that formation of 7-oxysterols might contribute to the toxicity of cholesteryl linoleate. The toxicity of triglycerides suggests that polyunsaturated fatty acid peroxidation products are also toxic. Possible mechanisms of cytotoxicity and relevance to atherosclerosis are discussed.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1993

The potential role of antioxidants in the prevention of atherosclerosis.

Hypercholesterolemia attributable to increased plasma concentrations of low density lipoproteins is a well recognized risk factor for the premature development of coronary atherosclerosis in both experimental animals and humans. Recent studies have indicated that modifications to low density lipoprotein result in enhanced uptake of the modified lipoproteins by macrophages and lead to accelerated rates of lipid deposition and the creation of foam cells. Oxidation of low density lipoprotein has been shown to be one of the modifications which leads to uptake of this lipoprotein by scavenger receptors present on macrophages and results in intracellular lipid accumulation. Treatment of hypercholesterolemic animals with antioxidant drugs, including probucol, has been shown to reduce the development of atherosclerosis and xanthoma regression has been observed in patients with severe hypercholesterolemia treated with this drug. Epidemiologic studies support the view that low plasma concentrations of antioxidant vitamins, including vitamin E are associated with higher rates of coronary atherosclerosis in humans and that supplementation with vitamin E is associated with a decreased incidence of coronary artery disease. Prospective clinical trials to assess the potential benefit of antioxidant supplementation in high risk patients are currently in progress and these trials, when completed, should provide definitive information concerning the potential benefits to be derived from supplementation with antioxidant vitamins as an adjunctive therapy to prevent the premature development of atherosclerosis.

Animals↗
PubMed2005

Influence of amla (Emblica officinalis Gaertn.) on hypercholesterolemia and lipid peroxidation in cholesterol-fed rats.

The effects of amla on low-density lipoprotein (LDL) oxidation and cholesterol levels were investigated in vitro and in vivo using Cu(2+)-induced LDL oxidation and cholesterol-fed rats. SunAmla and ethyl acetate (EtOAc) extract of amla significantly inhibited thiobarbituric acid (TBA)-reactive substance level in the Cu(2+)-induced LDL oxidation and the effects were stronger than those of probucol. In addition, the administration of SunAmla (at a dose of 20 or 40 mg/kg body weight/d) or EtOAc extract of amla (at a dose of 10 or 20 mg/kg body weight/d) for 20 d to rats fed 1% cholesterol diet significantly reduced total, free and LDL-cholesterol levels in a dose-dependent manner, and EtOAc extract of amla exhibited more potent serum cholesterol-lowering effect than SunAmla in the same amount. Furthermore, the oxidized LDL level in serum was markedly elevated in cholesterol-fed control rats as compared with normal rats, while it was significantly decreased by the administration of SunAmla or EtOAc extract of amla. Moreover, the serum TBA-reactive substance level was also significantly decreased after oral administration of SunAmla or EtOAc extract of amla. These results suggest that amla may be effective for hypercholesterolemia and prevention of atherosclerosis.

Animals↗
PubMed1991

Alcohols protect Escherichia coli against cold shock.

Alcohols protect Escherichia coli against cold shock, and the concentration of alcohol which provided optimal protection declined with increasing hydrophobicity of the alcohol. The rate of loss of viability after the chilling transition was decreased by n-octanol, even when it was added after that chilling transition. Cold-shocked cells exhibited a sensitivity toward dioxygen, seen as greater enumeration on anaerobic, rather than on aerobic, trypticase-yeast extract agar plates, and addition of catalase or antioxidants, such as alpha-tocopherol or probucol, to the agar plates did not lessen this dioxygen sensitivity. Respiratory capacity was diminished by cold shock, and cyanide-sensitive respiration was more affected than was cyanide-resistant respiration. Discharging the proton gradient, with the uncoupler carbonyl cyanide trifluoromethoxy-phenylhydrazone, did not change sensitivity to cold shock. There was no evidence for minimal medium recovery after cold shock. The data presented, as well as that already in the literature, are explained on the basis of membrane damage caused by patches of ordering transitions in one membrane leaflet, unmatched by comparable transitions in the mating leaflet.

1-Octanol↗
PubMed1992

Early pathological changes of endothelia in a model using LDL perfusion at physiological LDL-cholesterol concentration.

The aim of the present research was to provide further insight into the debated problem of the existence of modified LDL in vivo. For this purpose a novel model was devised for studying LDL injurious effect on endothelial cells (EC) by infusing native cholesterol rich LDL, diluted to physiological LDL cholesterol concentration. Normal rabbits were infused with LDL separated from rabbits previously fed either with standard food (I-LDL Group), 1% cholesterol (II-LDL Group) or 1% cholesterol plus probucol (IV-LDL Group). Cu++ modified II-LDL was infused as well (III-LDL Group). After dilution as above, lipid oxide (LP) significantly increased in III- and II-LDL media, as compared to I- and IV-LDL media. EC of III- and II-LDL Groups showed irregular shape and surface pattern. Further, they showed adhering clusters of monocytes, platelets and erythrocytes. Endocytic vesicles and ruthenium red-positive particles increased too. EC of IV-LDL Group were only slightly affected as compared to I-LDL Group. These data suggest that native LDL from hypercholesterolemic rabbits contain an oxidized form which is noxious to EC even when LDL is infused at physiological LDL-cholesterol concentration. This early injury is in part LP-associated and actively involves platelets and monocytes.

Animals↗
PubMed1996

A coronary primary intervention study of Japanese men: study design, implementation and baseline data. The Kyushu Lipid Intervention Study Group.

This report describes the design and baseline results of the Kyushu Lipid Intervention Study (KLIS). The study aims to test the hypothesis that the long term reduction of serum total cholesterol by pravastatin will lead to a decrease in coronary heart disease (CHD) events. The trial was designed to include a random 6,000 male patients aged 45-74 years with serum total cholesterol of 220 mg/dl (5.69 mmol/l) or greater and without a history of myocardial infarction, coronary surgery or angioplasty, to undertake either pravastatin or conventional treatment (including hypolipidemic drugs other than HMG CoA reductase inhibitors, probucol and bezafibrate), and to follow up each patient for 5 years. Primary endpoints are fatal and nonfatal myocardial infarction, coronary bypass surgery and angioplasty, cardiac death, and sudden and unexpected death. During the period from May 1990 to September 1993, a total of 5,640 male patients aged 45-74 were recruited by 902 participating physicians throughout Kyushu. Randomization was, however, neglected by study physicians; the numbers of patients enrolled were 3,061 in the pravastatin group and 2,579 in the conventional treatment group. Patients allocated to the pravastatin treatment were generally unfavorable regarding coronary risk factors. Baseline mean levels of serum total cholesterol were 259 mg/dl (6.70 mmol/l) in the pravastatin group and 246 mg/dl (6.36 mmol/l) in the conventional treatment group (p <0.001). Although the trial was regarded as a prospective observational study, the KLIS provides valuable quantitative data regarding cholesterol lowering and reduction in CHD events as well as safety data of the long-term use of a statin in Japanese men with hypercholesterolemia.

Aged↗
PubMed2000

Antioxidative effects of Choi-oki-to and its ability to inhibit the progression of atheroma in KHC rabbits.

Agents which inhibit the oxidative modification of low density lipoprotein (LDL) have been thought to be helpful in preventing the formation of atherosclerotic lesions; the so called "oxidation hypothesis". To test this hypothesis, we examined the antioxidative activities of 127 Kampo medicines in vitro and their inhibitory effects on the development of atheromatous plaque formation in KHC rabbits, a model of spontaneous familial hypercholesterolemia. Some of the 127 Kampo medicines showed scavenging or antioxidative effects equal to or stronger than those of probucol in vitro. Choi joki to, which had the strongest antioxidative effects on LDL in vitro, was chosen for a study in vivo. After 24 weeks, 1 g/kg of Choi joki to successfully inhibited the progression of atherosclerotic lesions in KHC rabbits (P < 0.01). Further investigations regarding the antioxidative effects of Kampo medicines are expected.

Animals↗
PubMed1998

In vitro inhibition by estrogens of the oxidative modifications of human lipoproteins.

Estrogens exert protective actions against atherosclerosis, part of these effects having been ascribed to their antioxidant properties. The aim of this work was to assess the ability of estrogens to prevent the oxidative modifications of low density lipoproteins (LDL) and other plasma lipoprotein fractions whose relationship with atherosclerosis has been less studied. For this purpose, different estrogen compounds were used: natural and synthetic estrogens, and catecholestrogens. The molecules were added in vitro to human LDL and very low density lipoproteins (VLDL) in the presence of Cu2+. The lipoprotein oxidative modifications were determined by measuring the formation of thiobarbituric acid reactive substances, the appearance of conjugated dienes and the degradation of tryptophan groups from the apoproteins. In VLDL, 2-hydroxyestradiol and diethylstilbestrol exerted potent antioxidant effects similar to those found for alpha-tocopherol and probucol. 17beta-Estradiol and 4-hydroxyestradiol also prevented VLDL oxidation, but to a lesser extent. When LDL were used, estrogens similarly exerted antioxidant actions, 2-hydroxyestradiol being the most potent inhibitor. These results show that estrogens, whose antioxidant actions have been demonstrated in other experimental models, also possess the ability to prevent in vitro the oxidative modifications of human plasma LDL and VLDL.

Cholesterol↗
PubMed1999

[Anti-hyperlipidemic drug].

Drug treatment of hyperlipidemia was reviewed. In the first part, mode of action, efficacy and safety of lipid-lowering agents were described and in the second part, strategies for treatment of hyperlipidemia was described. Treatment of hypercholesterolemia should be started with statin and if the reduction is not enough, cholestimide or nicotinic acid or probucol can be added. Mild hypertriglyceridemia can be treated with dextran sulfate sodium, but usually low dose of fenofibrate or bezafibrate will be necessary. For severe cases, combination therapy with fibrate and nicotinic acid or ethyl icosapentate is required. Treatment of combined hyperlipidemia should be started with fibrate, but when the increment of cholesterol is superior to triglyceride, statin can be chosen. If these drugs are not fully effective, combination therapy with statin and ethyl icosapentate is recommended.

Humans↗
PubMed1999

Coronary ectasia in familial hypercholesterolemia: histopathologic study regarding matrix metalloproteinases.

A 39-year-old male heterozygous familial hypercholesterolemia patient with marked ectasia over the entire coronary artery tree had been treated with several kinds of lipid-lowering single or combined drug therapies using clofibrate, compactin, cholestyramine, probucol, and pravastatin, and LDL-apheresis. During the 19-year follow-up, he suffered myocardial infarction three times and some of the ectatic coronary segments became enlarged, others narrowed, and one of them occluded in spite of the treatment. At the age of 58, he died after a fourth cardiac attack and subsequent cardiogenic shock. The autopsy indicated that his three coronary arteries showed diffuse ectatic changes and the largest lumen diameter of the left anterior descending artery was 25 mm, of the circumflex artery 12 mm, and of the right coronary artery 13 mm. The ectatic artery wall was not thick and the major part of the lumen was occupied by organized thrombi. Microscopic examinations showed that the larger the diameter of the lumen, the more severe the structural damage of the intima and tunica media and the larger the number of infiltrated cells, including lymphocytes, macrophages, and plasma cells. Immunoreactivity against matrix metalloproteinase (MMP)-1, and MMP-2 was observed in smooth muscle cells, macrophages, lymphocytes, and endothelial cells of the vasa vasorum or neovasculature. MMP-9 immunoreactivity was also localized in intimal foamy macrophages and round cells (macrophages and lymphocytes) of the media and adventitia. MMP-1 increased with the lumen diameter of the ectatic arteries. The ratio of immunoreactivity against both MMP-2 and MMP-9 to that against tissue inhibitor of metalloproteinase (TIMP)-2 also increased with the lumen diameter, but it no longer increased when the diameter was over 10 mm. These observations suggest that the MMP-TIMP system appears to play a significant role in the development of coronary ectasia

Adult↗
PubMed1999

Modulation of free radical stress in human red blood cell membrane by forskolin and the prospects for treatment of cardiovascular disease and diabetes.

This study has examined the effect of oxidants and elevated levels of glucose on membrane lipid peroxidation of human red blood calls (RBC). Washed RBC incubated with varying concentrations of glucose at 37 degrees C for 24 hrs. showed a significant increased membrane lipid peroxidation when compared with control RBC. Addition of ferrous sulphate and ascorbic acid which are known oxidants caused greater rise in lipid peroxides compared to elevated level of glucose alone. Pre-treatment of RBC with varying doses of forskolin (4-70 microg) was associated with significantly smaller rise in lipid peroxides in a dose dependent manner. Forskolin effect was comparable with the antioxidant effect of other drugs such as vitamin E, trimetazidine, ginkocer, probucol. It is possible that forskolin at higher concentrations may have a greater antioxidant effect than other antioxidant drug. However more studies, especially animal experiments, and trials in human would be necessary to confirm our findings.

Antioxidants↗
PubMed2000

Pharmacogenetics: a molecular sophistication or a new clinical tool for cardiologists?

The study of genetic risk factors for multifactorial diseases is attracting increasing interest. In particular interest has been focused on the interaction between genetic polymorphisms and environmental factors in determining the risk of disease. Among environmental factors therapeutic approaches should be considered. Therapeutic responses to a given drug, failure of drug efficacy, interindividual variability in side effects and toxicity of drugs could be at least partially accounted for by genetic polymorphisms. This paper summarizes the presently available applications of genetic concepts to some drugs commonly used in patients with cardiovascular disease. Statins and probucol fail to lower cholesterol levels in carriers of specific polymorphisms. The progression of cardiovascular disease is decreased by pravastatin only when certain polymorphisms are present. Induction problems and bleeding complications of warfarin occur in subgroups of populations carrying specific genetic variants of key enzymes in the drug metabolism. A new interpretation of the results of a thrombosis prevention trial will be given in the light of a genetic approach to pharmacology; indeed, prevention and treatment of thrombotic disease could be better focused on the basis of this knowledge. Future clinical trials and cost-effectiveness evaluation of drugs should be conducted taking these gene-drug interactions into account.

Administration, Oral↗
PubMed2000

Remodeling and Restenosis: Observations from Serial Intravascular Ultrasound Studies.

Late responses to nonstent coronary interventions are determined less by intimal hyperplasia than by the direction and magnitude of arterial remodeling, except in diabetic patients. Negative arterial remodeling is a late event, is often preceded by an early (nonsustained) positive remodeling, and is distinct from passive elastic recoil. Diabetic patients have an exaggerated intimal hyperplastic response. Plaque burden may play an important role in the restenosis process by amplifying the negative remodeling. Stents reduce restenosis by opposing the late negative remodeling to offset a stent-related increase in neointimal hyperplasia. Both probucol and radiation appear to reduce late lumen loss after balloon angioplasty by promoting positive remodeling.

Journal Article↗
PubMed2000

Anti-restenosis Trials.

The high frequency of restenosis after percutaneous coronary angioplasty is still a major clinical problem. It occurs in 30% to 60% of patients and limits the long-term success of angioplasty. Many clinical trials have been conducted to resolve this problem, using a wide range of pharmacologic agents such as antiplatelet agents, anticoagulation drugs, lipid-lowering drugs, angiotensin-converting enzyme inhibitors, anti-inflammatory drugs, and antiproliferative drugs. Thus far, no effective drug has been reported, with the exception of probucol, which unfortunately is not approved by the US Food and Drug Administration because it prolongs the QT time, and possibly trapidil and cilostazol, two agents that are currently being tested in larger trials. Stent implantation has significantly reduced the frequency of restenosis in patients with 1) short lesions in large coronary arteries, (> 3.0 mm), 2) native coronary restenosis lesions, 3) venous bypass graft obstructions, 4) chronic total occlusions, and 5) acute myocardial infarction in patients referred for primary percutaneous intervention. A significant problem is the occurrence of in-stent restenosis because it is associated with a high recurrence of restenosis, after repeat coronary intervention irrespective of the technique or device used. Brachytherapy may limit this problem. The high restenosis rate occurring in long lesions and in small vessels still remains an unresolved issue.

Journal Article↗
PubMed2001

Allergic reactions at repeat femoral angiography with ioxaglate.

PURPOSE: To study the occurrence of allergy-like reactions at angiography, repeated several times, and, secondly, to evaluate the effect of prophylactic treatment in individuals who had earlier experienced such reactions. MATERIAL AND METHODS: One hundred and fifty-seven patients with hypercholesterolaemia, participating in the Probucol Quantitative Regression Swedish Trial (PQRST), underwent aortofemoral angiography with ioxaglate (Hexabrix) repeated annually for 3 years. Allergic reactions to the contrast medium were recorded. At the following angiographies, all patients who had earlier experienced such reactions were treated prophylactically with steroids and antihistamine. RESULTS: Allergic reactions were observed in 35 patients. Twelve reacted only year 0, 3 only year 1, 5 only year 2 and 6 only year 3. Eight patients had at least one reaction also when treated prophylactically. It was significantly (p<0.05) more common to react at year 0 but not at year 1 than to react at year 1 but not at year 0. At years 1, 2 and 3 the frequency of reactions was significantly greater in the group given prophylactic treatment than in the group without any earlier reaction at all: 8/20 versus 3/137, 4/23 versus 6/134, and 6/29 versus 6/128, respectively. CONCLUSION: Some individuals had an increased risk of an allergy-like reaction to the contrast agent. Prophylactic treatment reduced the risk of renewed reactions, but not to the same level as for those without earlier reaction. Nevertheless, individuals who have had earlier reactions can be investigated in the future, with prophylactic treatment.

Adult↗