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Medicine Mar 2023Preventing contrast-induced acute kidney injury (CI-AKI) is critical because of its association with poor clinical outcomes, including extended hospital stays and... (Meta-Analysis)
Meta-Analysis
Preventing contrast-induced acute kidney injury with probucol and hydration in patients with coronary heart disease: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Preventing contrast-induced acute kidney injury (CI-AKI) is critical because of its association with poor clinical outcomes, including extended hospital stays and increased mortality. The effects of probucol on preventing CI-AKI have been controversial. Therefore, this systematic review and meta-analysis evaluated the influence of probucol combined with hydration on the CI-AKI risk in patients with coronary heart disease undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI).
METHODS
We retrieved data from the following databases from their inception to May 29, 2022: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database (Sinomed), Wanfang Database, and Chinese Scientific Journal Database. The methodological quality of the trials was assessed following the Cochrane Handbook guidelines, and Review Manager 5.3 and Stata 14.0 software were used for the data analysis.
RESULTS
We included 14 trials comprising 3306 patients in the analysis. All included trials reported the CI-AKI incidence rate (the primary outcome). Probucol with hydration significantly reduced the CI-AKI incidence compared to hydration alone (odds ratio [OR]: 0.33, 95% confidence interval [CI]: 0.25-0.44, P < .001). Subgroup analyses were performed based on the contrast medium type (iso-osmolality vs low-osmolality contrast medium [LOCM]) and volume (less than or more than 200 mL); the effects of probucol with hydration versus hydration-only on CI-AKI were comparable within each subgroup. Additionally, the serum creatinine (Scr) concentration 24 hours, 48 hours, and 72 hours and the estimated glomerular filtration rate (eGFR) 72 hours after contrast exposure were better in the probucol with hydration group than the hydration-only group. Finally, major clinical adverse events and adverse drug reactions were comparable between the probucol with hydration and hydration-only groups.
CONCLUSION
Probucol with hydration decreases the CI-AKI incidence compared to hydration only in patients with coronary heart disease undergoing CAG or PCI. However, more high-quality, large-sample, multicenter randomized trials are needed to confirm this conclusion.
Topics: Humans; Probucol; Contrast Media; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Coronary Angiography; Coronary Disease; Drug-Related Side Effects and Adverse Reactions; Acute Kidney Injury; Risk Factors; Multicenter Studies as Topic
PubMed: 36930109
DOI: 10.1097/MD.0000000000033273 -
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 -
PloS One 2019Type 2 diabetes (T2D) is characterised by β-cell damage and hyperglycaemia. The lipophilic drug, probucol, has shown significant β-cell protective and potential...
An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques.
Type 2 diabetes (T2D) is characterised by β-cell damage and hyperglycaemia. The lipophilic drug, probucol, has shown significant β-cell protective and potential antidiabetic effects, which were enhanced by hydrophilic bile acid incorporation using taurocholic acid and chenodeoxycholic acid. However, probucol has severe cardiotoxicity and a variable absorption profile, which limit its potential applications in T2D. Accordingly, this study aimed to design multiple formulations to optimise probucol oral delivery in T2D and test their effects on probucol absorption and accumulation in the heart. Adult male mice were given a high fat diet (HFD), and a week later, injected with a single dose of alloxan to accelerate T2D development, and once diabetes confirmed, divided into three groups (six to seven mice each). The groups were gavaged a daily dose of probucol powder, probucol microcapsules, or probucol-bile acid microcapsules for three months, and euthanized; and blood, tissues, and feces collected for blood glucose and probucol concentration analyses. Probucol concentrations in plasma were similar among all the groups. Groups given probucol microcapsules and probucol-bile acid microcapsules showed significant reduction in probucol accumulation in the heart compared with the group given probucol powder (p<0.05). Probucol microencapsulation with or without bile acids reduced its accumulation in heart tissues, without changing plasma concentrations, which may be beneficial in reducing its cardiotoxicity and optimise its potential applications in T2D.
Topics: Administration, Oral; Animals; Capsules; Cardiotoxicity; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Fats; Male; Mice; Mice, Inbred BALB C; Myocardium; Probucol
PubMed: 30947243
DOI: 10.1371/journal.pone.0214984 -
Asian Journal of Pharmaceutical Sciences Nov 2019The objective of this work is to construct a nanosuspension drug delivery system of probucol, a BCS II drug, in order to improve its dissolution and oral...
The objective of this work is to construct a nanosuspension drug delivery system of probucol, a BCS II drug, in order to improve its dissolution and oral bioavailability. The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process. Cellulose derivatives of different substitution groups and molecular weights, including HPMC, HPC, and MC, were evaluated as the primary stabilizer of probucol nanosuspension. Ternary stabilizers system composed of a primary stabilizer (cellulose derivative, HPC), a nonionic surfactant (Pluronic® F68), and an anionic surfactant (SDS) was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media. The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4 °C or 25 °C. The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate (> 60% at 2 h) compared to other cryoprotectant. The pharmacokinetic evaluation indicated about 15-folds higher value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats. The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.
PubMed: 32104491
DOI: 10.1016/j.ajps.2018.12.001 -
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 -
Canadian Medical Association Journal Sep 1980
Topics: Adult; Aged; Cholesterol; Cholesterol, HDL; Humans; Hyperlipoproteinemia Type II; Lipoproteins, HDL; Middle Aged; Phenols; Probucol
PubMed: 7260778
DOI: No ID Found -
European Journal of Pharmacology Aug 2017Probucol 4,4'- (Isopropylidenedithio)bis(2,6-di-tert-butylphenol) is a synthetic molecule clinically used for prevention and treatment of hypercholesterolemia and...
Probucol 4,4'- (Isopropylidenedithio)bis(2,6-di-tert-butylphenol) is a synthetic molecule clinically used for prevention and treatment of hypercholesterolemia and atherosclerosis. Recent studies have shown that the beneficial effects of probucol mainly derive from its anti-inflammatory and antioxidant properties. Gram-negative bacteria are common infectious agents and their wall components, e.g. lipopolysaccharide (LPS), are important elicitors of inflammation. LPS is sensed by tissue resident cells and it triggers a Toll-like receptor 4/MyD88-dependent signaling cascade resulting in endothelial activation, leukocyte recruitment and nociception. Therefore the present study aimed to investigate the anti-inflammatory and analgesic effects of probucol in models of LPS-induced acute inflammation. Probucol at 0.3-30mg/kg was administrated to male Swiss mice per oral 1h before intraplantar or intraperitoneal lipopolysaccharide stimulus. Probucol at 3mg/kg reduced lipopolysaccharide-induced mechanical and thermal hyperalgesia. These effects were accompanied by reduced leukocyte influx and cytokine production in both paw skin and peritoneum exudate. Unexpectedly, probucol did not alter lipopolysaccharide-induced tissue oxidative stress at anti-inflammatory /analgesic dose. On the other hand, probucol inhibited lipopolysaccharide-induced nuclear factor kappa B (NF-кB) activation in paw tissue as well as NF-кB activity in cultured macrophages in vitro, reinforcing the inhibitory effect of probucol over the NF-кB signaling pathway. In this sense, we propose that probucol acts on resident immune cells, such as macrophages, targeting the NF-кB pathway. As a result, it prevents the amplification and persistence of the inflammatory response by attenuating NF-кB-dependent cytokine production and leukocyte recruitment explaining its analgesic effects as well.
Topics: Animals; Cytokines; Hyperalgesia; Inflammation; Leukocytes; Lipopolysaccharides; Macrophages; Male; Mice; NF-kappa B; Peritoneal Cavity; Probucol; RAW 264.7 Cells
PubMed: 28501577
DOI: 10.1016/j.ejphar.2017.05.016 -
Biomedicine & Pharmacotherapy =... Jan 2019We have investigated the possible effects and mechanism of atorvastatin, a statin, and/or probucol, a powerful antioxidant used to lower cholesterol before 1995, on the...
INTRODUCTION
We have investigated the possible effects and mechanism of atorvastatin, a statin, and/or probucol, a powerful antioxidant used to lower cholesterol before 1995, on the atherosclerosis development.
METHODS
Apolipoprotein-E-deficient (ApoE) mice fed with the high fat diet were randomly divided into 3 groups (n = 10/each group): Placebo, Atorvastatin (10 mg/ kg/d), and atorvastatin (10 mg/kg/d) plus probucol (10 mg/kg/d) groups. C57BL/6 J mice were fed with normal diet as the control group (n = 10). Animals were sacrificed 10 weeks after the intervention. To evaluate the experimental atherosclerosis, blood tests were used for measuring serum lipoprotein profile, Western blots for endoplasmic reticulum (ER) stress protein expression, H&E staining for plaque lesions, immunohistology for macrophages, inflammatory cytokines, innate immune receptor TLR-4, transcription factor NF-κB, and atherosclerosis plaques.
RESULTS
Compared with the control group, ApoE mice in the placebo group showed with the significantly (p < 0.05) higher levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and oxidized low density lipoprotein (ox-LDL), PERK, GRP78, CHOP, IL-1β, TNF-α and NF-κB, but with the lower levels of high-density lipoprotein cholesterol (HDL) and TLR-4, and also the increase in macrophages and the aortic media collagen, and the decrease in the elastic fibers (p < 0.01). Treatment with atorvastatin recovered all these features (p < 0.05 or p < 0.01) near to the levels in the control group. In addition, the combination of atorvastatin and probucol has shown the slightly stronger effect than the use of atorvastatin alone without statistical significances when comparing most bio-markers of atherosclerosis, but with significant differences in the reduction of the plaque lesion areas and macrophages (p < 0.05).
CONCLUSIONS
Atorvastatin and/or probucol suppresses ER stress and increase the level of TLR-4, which lowers NF-κB, resulting in the recovery of atherosclerosis in the ApoE mouse model.
Topics: Animals; Antioxidants; Apolipoproteins E; Atherosclerosis; Atorvastatin; Cholesterol; Cytokines; Diet, High-Fat; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Inflammation; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Plaque, Atherosclerotic; Probucol
PubMed: 30551396
DOI: 10.1016/j.biopha.2018.10.184 -
Pharmaceutics Aug 2021A major obstacle in islet transplantation and graft survival pre and post transplantation is islet apoptosis due to mainly inflammatory bio molecules released during...
Probucol Pharmacological and Bio-Nanotechnological Effects on Surgically Transplanted Graft Due to Powerful Anti-Inflammatory, Anti-Fibrotic and Potential Bile Acid Modulatory Actions.
INTRODUCTION
A major obstacle in islet transplantation and graft survival pre and post transplantation is islet apoptosis due to mainly inflammatory bio molecules released during islet harvesting and post graft transplantation and hence, subsequent graft fibrosis and failure. This study aimed to investigate if incorporation of the anti-inflammatory anti-hyperlipidaemic drug probucol (PB) would improve islet-graft survival and function, post transplantation in Type 1 diabetes (T1D).
METHODS
T1D was induced in mice, and biological profiles of the diabetic mice transplanted PB-microencapsulated islets harvested from healthy syngeneic mice were measured.
RESULTS AND CONCLUSION
Compared with sham (no PB), the treated group showed significant reduction in serum levels of interleukin-1β, interleukin-6, interleukin-12, interleukin-17, and tumour necrosis factor-α, accompanied by a 3-fold increase in survival duration, which suggests PB islet-protective effects, post transplantation.
PubMed: 34452266
DOI: 10.3390/pharmaceutics13081304 -
Acta Pharmacologica Sinica Aug 2016Increasing evidence suggests that probucol, a lipid-lowering agent with anti-oxidant activities, may be useful for the treatment of ischemic stroke with hyperlipidemia...
AIM
Increasing evidence suggests that probucol, a lipid-lowering agent with anti-oxidant activities, may be useful for the treatment of ischemic stroke with hyperlipidemia via reduction in cholesterol and neuroinflammation. In this study we examined whether probucol could protect against brain ischemic injury via anti-neuroinflammatory action in normal and hyperlipidemic mice.
METHODS
Primary mouse microglia and murine BV2 microglia were exposed to lipopolysaccharide (LPS) for 3 h, and the release NO, PGE2, IL-1β and IL-6, as well as the changes in NF-κB, MAPK and AP-1 signaling pathways were assessed. ApoE KO mice were fed a high-fat diet containing 0.004%, 0.02%, 0.1% (wt/wt) probucol for 10 weeks, whereas normal C57BL/6J mice received probucol (3, 10, 30 mg·kg(-1)·d(-1), po) for 4 d. Then all the mice were subjected to focal cerebral ischemia through middle cerebral artery occlusion (MCAO). The neurological deficits were scored 24 h after the surgery, and then brains were removed for measuring the cerebral infarct size and the production of pro-inflammatory mediators.
RESULTS
In LPS-treated BV2 cells and primary microglial cells, pretreatment with probucol (1, 5, 10 μmol/L) dose-dependently inhibited the release of NO, PGE2, IL-1β and IL-6, which occurred at the transcription levels. Furthermore, the inhibitory actions of probucol were associated with the downregulation of the NF-κB, MAPK and AP-1 signaling pathways. In the normal mice with MCAO, pre-administration of probucol dose-dependently decreased the infarct volume and improved neurological function. These effects were accompanied by the decreased production of pro-inflammatory mediators (iNOS, COX-2, IL-1, IL-6). In ApoE KO mice fed a high-fat diet, pre-administration of 0.1% probucol significantly reduced the infarct volume, improved the neurological deficits following MCAO, and decreased the total- and LDL-cholesterol levels.
CONCLUSION
Probucol inhibits LPS-induced microglia activation and ameliorates cerebral ischemic injury in normal and hyperlipidemic mice via its anti-neuroinflammatory actions, suggesting that probucol has potential for the treatment of patients with or at risk for ischemic stroke and hyperlipidemia.
Topics: Animals; Apolipoproteins E; Brain Ischemia; Diet, High-Fat; Dinoprostone; Dose-Response Relationship, Drug; Hyperlipidemias; Infarction; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Male; Mice; Mice, Knockout; Microglia; Nitric Oxide; Primary Cell Culture; Probucol; Signal Transduction
PubMed: 27345627
DOI: 10.1038/aps.2016.51