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Lipids in Health and Disease Nov 2011Probucol is a unique hypolipidemic agent that decreases high density lipoprotein cholesterol (HDL-C). However, it is not definite that whether probucol hinders the...
BACKGROUND
Probucol is a unique hypolipidemic agent that decreases high density lipoprotein cholesterol (HDL-C). However, it is not definite that whether probucol hinders the progression of atherosclerosis by improving HDL function.
METHODS
Eighteen New Zealand White rabbits were randomly divided into the control, atherosclerosis and probucol groups. Control group were fed a regular diet; the atherosclerosis group received a high fat diet, and the probucol group received the high fat diet plus probucol. Hepatocytes and peritoneal macrophages were isolated for [(3)H] labeled cholesterol efflux rates and expression of ABCA1 and SR-B1 at gene and protein levels; venous blood was collected for serum paraoxonase 1, myeloperoxidase activity and lipid analysis. Aorta were prepared for morphologic and immunohistochemical analysis after 12 weeks.
RESULTS
Compared to the atherosclerosis group, the paraoxonase 1 activity, cholesterol efflux rates, expression of ABCA1 and SR-BI in hepatocytes and peritoneal macrophages, and the level of ABCA1 and SR-BI in aortic lesions were remarkably improved in the probucol group, But the serum HDL cholesterol concentration, myeloperoxidase activity, the IMT and the percentage plaque area of aorta were significantly decreased.
CONCLUSION
Probucol alleviated atherosclerosis by improving HDL function. The mechanisms include accelerating the process of reverse cholesterol transport, improving the anti-inflammatory and anti-oxidant functions.
Topics: ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; Animals; Anticholesteremic Agents; Aorta; Aryldialkylphosphatase; Atherosclerosis; CD36 Antigens; Cells, Cultured; Cholesterol; Diet, High-Fat; Gene Expression; Hepatocytes; Lipoproteins, HDL; Liver; Macrophages, Peritoneal; Male; Peroxidase; Probucol; Rabbits; Random Allocation; Tunica Intima; Up-Regulation
PubMed: 22078494
DOI: 10.1186/1476-511X-10-210 -
Frontiers in Neuroscience 2024Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related...
Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.
PubMed: 38716255
DOI: 10.3389/fnins.2024.1368552 -
Journal of Atherosclerosis and... Jan 2020
Topics: ATP Binding Cassette Transporter 1; Animals; Cholesterol, HDL; Female; Fertility; Lecithin Cholesterol Acyltransferase Deficiency; Male; Mice; Probucol; Scavenger Receptors, Class B
PubMed: 31484853
DOI: 10.5551/jat.ED115 -
Drugs Oct 1991A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology... (Review)
Review
A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology of more than 50 human diseases. Radicals and other reactive oxygen species are formed constantly in the human body, both by deliberate synthesis (e.g. by activated phagocytes) and by chemical side-reactions. They are removed by enzymic and nonenzymic antioxidant defence systems. Oxidative stress, occurring when antioxidant defences are inadequate, can damage lipids, proteins, carbohydrates and DNA. A few clinical conditions are caused by oxidative stress, but more often the stress results from the disease. Sometimes it then makes a significant contribution to the disease pathology, and sometimes it does not. Several antioxidants are available for therapeutic use. They include molecules naturally present in the body [superoxide dismutase (SOD), alpha-tocopherol, glutathione and its precursors, ascorbic acid, adenosine, lactoferrin and carotenoids] as well as synthetic antioxidants [such as thiols, ebselen (PZ51), xanthine oxidase inhibitors, inhibitors of phagocyte function, iron ion chelators and probucol]. The therapeutic efficacy of SOD, alpha-tocopherol and ascorbic acid in the treatment of human disease is generally unimpressive to date although dietary deficiencies of the last two molecules should certainly be avoided. Xanthine oxidase inhibitors may be of limited relevance as antioxidants for human use. Exciting preliminary results with probucol (antiatherosclerosis), ebselen (anti-inflammatory), and iron ion chelators (in thalassaemia, leukaemia, malaria, stroke, traumatic brain injury and haemorrhagic shock) need to be confirmed by controlled clinical trials. Clinical testing of N-acetylcysteine in HIV-1-positive subjects may also be merited. A few drugs already in clinical use may have some antioxidant properties, but this ability is not widespread and drug-derived radicals may occasionally cause significant damage.
Topics: Animals; Antioxidants; Free Radicals; Humans
PubMed: 1723362
DOI: 10.2165/00003495-199142040-00003 -
Asian Journal of Andrology 2022[This corrects the article DOI: 10.4103/aja.aja_89_19].
[This corrects the article DOI: 10.4103/aja.aja_89_19].
PubMed: 34747728
DOI: 10.4103/aja202187 -
International Journal of Molecular... Dec 2018Although epidemiological and experimental studies have suggested beneficial effects of vitamin E deficiency on malaria infection, it has not been clinically applicable... (Review)
Review
Although epidemiological and experimental studies have suggested beneficial effects of vitamin E deficiency on malaria infection, it has not been clinically applicable for the treatment of malaria owing to the significant content of vitamin E in our daily food. However, since α-tocopherol transfer protein (α-TTP) has been shown to be a determinant of vitamin E level in circulation, manipulation of α-tocopherol levels by α-TTP inhibition was considered as a potential therapeutic strategy for malaria. Knockout studies in mice indicated that inhibition of α-TTP confers resistance against malaria infections in murines, accompanied by oxidative stress-induced DNA damage in the parasite, arising from vitamin E deficiency. Combination therapy with chloroquine and α-TTP inhibition significantly improved the survival rates in murines with malaria. Thus, clinical application of α-tocopherol deficiency could be possible, provided that α-tocopherol concentration in circulation is reduced. Probucol, a recently found drug, induced α-tocopherol deficiency in circulation and was effective against murine malaria. Currently, treatment of malaria relies on the artemisinin-based combination therapy (ACT); however, when mice infected with malarial parasites were treated with probucol and dihydroartemisinin, the beneficial effect of ACT was pronounced. Protective effects of vitamin E deficiency might be extended to manage other parasites in future.
Topics: Animals; Antimalarials; Artemisinins; Carrier Proteins; Cytokines; Malaria; Oxidative Stress; Vitamin E; Vitamin E Deficiency; alpha-Tocopherol
PubMed: 30586912
DOI: 10.3390/ijms20010064 -
Diabetes & Vascular Disease Research Jan 2019An emerging body of evidence consistently suggests that compromised blood-brain barrier integrity may be causally associated with cognitive decline induced by type-2... (Comparative Study)
Comparative Study
An emerging body of evidence consistently suggests that compromised blood-brain barrier integrity may be causally associated with cognitive decline induced by type-2 diabetes. Our previous studies demonstrated that selected anti-inflammatory/anti-oxidative agents can preserve the integrity of blood-brain barrier and prevent neuroinflammation in mouse models of dysfunctional blood-brain barrier. Therefore, we have tested whether the previously proven blood-brain barrier protective agent, probucol, can prevent blood-brain barrier breakdown and cognitive decline in a dietary-induced murine model of diabetic insulin resistance. After 6-month chronic ingestion of a diet high in fat and fructose, the mice became insulin resistant. The high-fat and high-fructose-fed mice showed significant cognitive decline assessed by Morris water maze, concomitant with significant elevations in cortical and hippocampal glial acidic fibrillary protein and Fluoro Jade-C staining, indicating heightened neuroinflammation and neurodegeneration, respectively. The integrity of blood-brain barrier in high-fat and high-fructose-fed mice was substantially compromised, and this showed a significant association with heightened neurodegeneration. Co-provision of probucol with high-fat and high-fructose diet completely prevented the cognitive decline and blood-brain barrier dysfunction. Similarly, metformin was able to restore the cognitive function in high-fat and high-fructose-fed mice, while its blood-brain barrier protective effects were modest. These data suggest that probucol may prevent cognitive decline induced by insulin resistance by preserving the integrity of blood-brain barrier, whereas metformin's neuroprotective effects may be mediated through a separate pathway.
Topics: Animals; Anti-Inflammatory Agents; Behavior, Animal; Blood-Brain Barrier; Cerebral Cortex; Cognition; Cognition Disorders; Cytokines; Diabetes Mellitus, Experimental; Diet, High-Fat; Fructose; Glial Fibrillary Acidic Protein; Hippocampus; Hypoglycemic Agents; Inflammation Mediators; Insulin Resistance; Male; Maze Learning; Metformin; Mice, Inbred C57BL; Nerve Degeneration; Neuroprotective Agents; Probucol
PubMed: 30156119
DOI: 10.1177/1479164118795274 -
JACC. Cardiovascular Interventions Jun 2016This study sought to perform a systematic review and network meta-analysis to compare the relative safety and efficacy of contemporary DES and BVS. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study sought to perform a systematic review and network meta-analysis to compare the relative safety and efficacy of contemporary DES and BVS.
BACKGROUND
To improve outcomes of patients undergoing percutaneous coronary revascularization, there have been advances in the design of drug-eluting stents (DES), including the development of drug-eluting bioresorbable vascular scaffolds (BVS).
METHODS
Prospective, randomized, controlled trials comparing bare-metal stents (BMS), paclitaxel-eluting stents (PES), sirolimus-eluting stents (SES), Endeavor zotarolimus-eluting stents (E-ZES), cobalt-chromium (CoCr) everolimus-eluting stents (EES), platinum-chromium (PtCr)-EES, biodegradable polymer (BP)-EES, Resolute zotarolimus-eluting stents (R-ZES), BP biolimus-eluting stents (BP-BES), hybrid sirolimus-eluting stents (H [Orsiro]-SES), polymer-free sirolimus- and probucol-eluting stents, or BVS were searched in online databases. The primary endpoint was definite or probable stent thrombosis at 1 year.
RESULTS
A total of 147 trials including 126,526 patients were analyzed in this study. All contemporary DES were superior to BMS and PES in terms of definite or probable stent thrombosis at 1 year. CoCr-EES, PtCr-EES, and H-SES were associated with significantly lower risk than BVS. CoCr-EES and H-SES were superior to SES and BP-BES. The risk of myocardial infarction was significantly lower with H-SES than with BVS. There were no significant differences regarding all-cause or cardiac mortality. Contemporary devices including BVS showed comparably low risks of repeat revascularization.
CONCLUSIONS
Contemporary DES, including biocompatible DP-DES, BP-DES, and polymer-free DES, showed a low risk of definite or probable stent thrombosis at 1 year. BVS had an increased risk of device thrombosis compared with CoCr-EES, PtCr-EES, and H-SES. Data from extended follow-up are warranted to confirm the long-term safety of contemporary coronary devices.
Topics: Absorbable Implants; Bayes Theorem; Coronary Disease; Coronary Thrombosis; Drug-Eluting Stents; Humans; Markov Chains; Monte Carlo Method; Network Meta-Analysis; Odds Ratio; Percutaneous Coronary Intervention; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 27262860
DOI: 10.1016/j.jcin.2016.03.038 -
Journal of Atherosclerosis and... Feb 2021Although intensive statin therapy reduced cardiovascular risks, cardiovascular events have not been completely prevented. Probucol is a potent antioxidant and reduces... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Although intensive statin therapy reduced cardiovascular risks, cardiovascular events have not been completely prevented. Probucol is a potent antioxidant and reduces tendon xanthomas in familial hypercholesterolemia patients despite reduction of high-density lipoprotein (HDL)-cholesterol (HDL-C). We investigated whether probucol can reduce cardiovascular events on top of conventional lipid-lowering therapy in patients with coronary heart disease (CHD).
METHODS
PROSPECTIVE is a multicenter, randomized, prospective study that recruited 876 Japanese patients with CHD and dyslipidemia with a low-density lipoprotein (LDL)-cholesterol (LDL-C) level of ≥ 140 mg/dL without medication or those treated with lipid-lowering drugs. Lipid-lowering agents were administered during the study period in the control group (n=438), and probucol 500 mg/day was added to lipid-lowering therapy in the probucol group (n=438). Patients were randomly assigned to two treatment groups by adjusting the LDL-C level and presence of diabetes and hypertension and followed up for more than 3 years. The primary end point was a composite of cerebrovascular and cardiovascular events (cardiovascular disease death including sudden death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or coronary revascularization). The secondary end point was carotid intima-media thickness in a subset of patients.
RESULTS
The incidence of the primary end point showed a trend to be lower in the probucol group compared with that in the control group despite reduced HDL-C without serious adverse events. Anti-atherogenic effects of probucol may be attributed to its potent antioxidative function and enhancement of reverse cholesterol transport.
CONCLUSION
Since there was no statistical significance between the probucol and control groups despite a marked reduction of HDL-C, further studies on the clinical outcomes of probucol on top of conventional therapy may be necessary in the future (UMIN000003307).
Topics: Aged; Anticholesteremic Agents; Antioxidants; Biological Transport; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cholesterol, HDL; Cholesterol, LDL; Drug Monitoring; Female; Humans; Hyperlipidemias; Male; Probucol; Secondary Prevention; Stroke; Treatment Outcome
PubMed: 32336695
DOI: 10.5551/jat.55327 -
Cordyceps sinensis prevents contrast-induced nephropathy in diabetic rats: its underlying mechanism.International Journal of Clinical and... 2018Apoptosis is recognized as an important mechanism in contrast-induced nephropathy (CIN). This study investigated the renal protective effect of cordyceps sinensis (CS)...
Apoptosis is recognized as an important mechanism in contrast-induced nephropathy (CIN). This study investigated the renal protective effect of cordyceps sinensis (CS) in a diabetic rat model of CIN and the mechanism of its effect. Sixty SD rats were randomly divided into 4 groups, the control group, model group, probucol group, and CS group. We used a diabetic rat model of Iodixanol-induced CIN. Serum creatinine (Scr), blood urea nitrogen (BUN), urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL) levels were measured to evaluate renal function. Total antioxidative ability (T-AOC), superoxide dismutase (SOD), and malonaldehyde (MDA) levels were assessed to discuss the effect of probucol and CS on oxidative stress. The pathologic changes in the kidney were observed by hematoxylin and eosin (HE) staining and periodic acid-Schiff (PAS) staining. Apoptosis was assessed by transmission electron microscopy and TUNEL staining. Caspase-3, Bax, Bcl2 and phospho-p38 mitogen-activated protein kinase (MAPK) protein expressions were assessed by Western blotting. The model group of rats showed significantly elevated levels of BUN, Scr, urinary KIM-1, NGAL, and parameters of oxidative stress (P<0.05). Both the probucol and CS groups demonstrated significantly lower Scr, BUN, and urinary KIM-1, NGAL levels compared to the model group (P<0.05), with no significant difference between these two groups. The probucol group and the CS group had significantly lower MDA and higher T-AOC, SOD than the model group after modeling (P<0.05). Caspase-3, Bax activation were effectively repressed while Bcl-2 expression was increased by probucol and CS pretreatment. Mechanistically, probucol and CS decreased the expression of JNK protein and increased the expression of ERK protein. CS can effectively reduce kidney damage caused by contrast medium. The underlying mechanism may be that CS accelerates the recovery of renal function and renal pathology by reducing local renal oxidative stress and influencing MAPK signal pathways.
PubMed: 31949644
DOI: No ID Found