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Fenofibrate

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https://www.readbyqxmd.com/read/28911687/simultaneous-separation-of-antihyperlipidemic-drugs-by-green-ultrahigh-performance-liquid-chromatography-diode-array-detector-method-improving-the-health-of-liquid-chromatography
#1
Mansoor Alghazi, Fars Alanazi, Kazi Mohsin, Nasir Ali Siddiqui, Faiyaz Shakeel, Nazrul Haq
Statins in combination with fibrates show beneficial effects on the lipoprotein profile of patients because they have positive complimentary effects on lipid profile. A new green ultrahigh-performance liquid chromatography-diode array detector method for simultaneous analysis of simvastatin (SMV) and fenofibrate (FNF) in standard form, marketed formulations, and self-emulsifying drug delivery system formulations was developed and validated in the present investigation. The method utilized C18 as stationary phase and a combination of methanol:water (8:2) as an eluent...
April 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28903946/ppara-agonist-fenofibrate-enhances-fatty-acid-%C3%AE-oxidation-and-attenuates-polycystic-kidney-and-liver-disease-in-mice
#2
Ronak Lakhia, Matanel Yheskel, Andrea Flaten, Ezekiel B Quittner-Strom, William L Holland, Vishal Patel
PPARA is nuclear hormone receptor that promotes fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS). We and others have recently shown that PPARA and its target genes are downregulated, and FAO and OXPHOS are impaired in autosomal dominant polycystic kidney disease (ADPKD). However, whether PPARA and FAO/OXPHOS are causally linked to ADPKD progression is not entirely clear. We report that expression of PPARA and FAO/OXPHOS genes is downregulated and in-vivo β-oxidation rate of 3H-labelled triolein is reduced in Pkd1RC/RC mice, a slowly-progressing orthologous model of ADPKD that closely mimics the human ADPKD phenotype...
September 13, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28898693/no-oxygen-no-glucose-no-problem-fatty-acid-catabolism-enhances-effector-cd8-tils
#3
Will Bailis, Justin A Shyer, Michael Chiorazzi, Richard A Flavell
The tumor microenvironment presents metabolic constraints to immunosurveiling cells. In this issue of Cancer Cell, Zhang et al. demonstrate that CD8(+) TILs reprogram under hypoxic and hypoglycemic conditions, regaining effector function by engaging fatty acid catabolism, which is promoted by fenofibrate and synergistic with immune checkpoint blockade therapy.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28874443/amelioration-of-diet-induced-steatohepatitis-in-mice-following-combined-therapy-with-aso-fsp27-and-fenofibrate
#4
Ananthi Rajamoorthi, Noemi Arias, Jeannine Basta, Richard G Lee, Ángel Baldán
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD progresses from benign steatosis to steatohepatitis (NASH) to cirrhosis, and is linked to hepatocellular carcinoma. No targeted treatment is currently approved for NAFLD/NASH. We showed that fat-specific protein 27 (FSP27), a lipid droplet-associated protein that controls triglyceride turnover in the hepatocyte, is required for fasting- and diet-induced triglyceride accumulation in the liver. However, silencing Fsp27 with antisense oligonucleotides (ASOs) did not improve hepatosteatosis in genetic nor nutritional mouse models of obesity...
September 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28871336/zoledronate-dysregulates-fatty-acid-metabolism-in-renal-tubular-epithelial-cells-to-induce-nephrotoxicity
#5
Lili Cheng, Mengmeng Ge, Zhou Lan, Zhilong Ma, Wenna Chi, Wenhua Kuang, Kun Sun, Xinbin Zhao, Ye Liu, Yaqian Feng, Yuedong Huang, Maoguo Luo, Liping Li, Bin Zhang, Xiaoyu Hu, Lina Xu, Xiaohui Liu, Yi Huo, Haiteng Deng, Jinliang Yang, Qiaoran Xi, Yonghui Zhang, Julie A Siegenthaler, Ligong Chen
Zoledronate is a bisphosphonate that is widely used in the treatment of metabolic bone diseases. However, zoledronate induces significant nephrotoxicity associated with acute tubular necrosis and renal fibrosis when administered intravenously. There is speculation that zoledronate-induced nephrotoxicity may result from its pharmacological activity as an inhibitor of the mevalonate pathway but the molecular mechanisms are not fully understood. In this report, human proximal tubular HK-2 cells and mouse models were combined to dissect the molecular pathways underlying nephropathy caused by zoledronate treatments...
September 4, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28866026/the-peroxisome-proliferator-activated-receptor-pan-agonist-bezafibrate-suppresses-microvascular-inflammatory-responses-of-retinal-endothelial-cells-and-vascular-endothelial-growth-factor-production-in-retinal-pigmented-epithelial-cells
#6
Ayumi Usui-Ouchi, Yasuo Ouchi, Nobuyuki Ebihara
A randomized clinical trial showed the beneficial effects of the selective peroxisome proliferator-activated receptor (PPAR)-α agonist, fenofibrate, in reducing the progression of diabetic retinopathy independent of serum lipid levels. All subtypes of PPAR (PPAR-α, PPAR-γ, and PPAR-β/δ) have been reported to play a key role in microvascular inflammation and angiogenesis. Therefore, the agonistic function of fenofibrate against the PPAR-α has been suggested to contribute to its medicinal effect. Furthermore, bezafibrate is a fibrate drug commonly used as a lipid-lowering agent to treat hyperlipidemia and acts as a pan-agonist of all PPARs subtypes...
August 31, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28855630/ppar%C3%AE-activation-protects-against-cholestatic-liver-injury
#7
Qi Zhao, Rui Yang, Jing Wang, Dan-Dan Hu, Fei Li
Intrahepatic cholestasis induced by drug toxicity, bile salt export pump (BSEP) deficiency, or pregnancy frequently causes cholestatic liver damage, which ultimately may lead to liver fibrosis and cirrhosis. Here, the preventive and therapeutic effects of peroxisome proliferator-activated receptor α (PPARα) signaling activated by fenofibrate was evaluated on cholestatic liver damage. Metabolomic analysis revealed that alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis resulted in the accumulation of serum long-chain acylcarnitines and triglyceride, and the reduced expression of four fatty acid β-oxidation (β-FAO) relevant genes (Cpt1b, Cpt2, Mcad and Hadha), indicating the disruption of β-FAO...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835163/an-epigenome-wide-association-study-of-inflammatory-response-to-fenofibrate-in-the-genetics-of-lipid-lowering-drugs-and-diet-network
#8
Nabiha Yusuf, Bertha Hidalgo, Marguerite R Irvin, Jin Sha, Degui Zhi, Hemant K Tiwari, Devin Absher, Donna K Arnett, Stella W Aslibekyan
AIM: Fenofibrate, a PPAR-α inhibitor used for treating dyslipidemia, has well-documented anti-inflammatory effects that vary between individuals. While DNA sequence variation explains some of the observed variability in response, epigenetic patterns present another promising avenue of inquiry due to the biological links between the PPAR-α pathway, homocysteine and S-adenosylmethionine - a source of methyl groups for the DNA methylation reaction. HYPOTHESIS: DNA methylation variation at baseline is associated with the inflammatory response to a short-term fenofibrate treatment...
September 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28817808/ppar%C3%AE-agonist-stimulated-angiogenesis-by-improving-endothelial-precursor-cell-function-via-a-nlrp3-inflammasome-pathway
#9
Yaping Deng, Xue Han, Zheng Yao, Yuannan Sun, Jiawen Yu, Jian Cai, Guofei Ren, Guojun Jiang, Feng Han
BACKGROUND: Impaired wound healing is a common complication of diabetes and is the leading cause of lower extremity amputation. Treatment with fenofibrate, a peroxisome proliferators-activated receptor α (PPARα) agonist, was associated with a lower risk of amputations, particularly minor amputations without known large-vessel diseases, probably through non-lipid mechanisms. The current study aimed to test our hypothesis that fenofibrate stimulates angiogenesis and restores endothelial precursor cell (EPC) function via inhibiting Nod-like receptor protein 3 (NLRP3) inflammasome in streptozotocin (STZ)-induced diabetic mice...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28807819/carrier-characteristics-influence-the-kinetics-of-passive-drug-loading-into-lipid-nanoemulsions
#10
Katrin Göke, Heike Bunjes
Passive loading as a novel screening approach is a material-saving tool for the efficient selection of a suitable colloidal lipid carrier system for poorly water soluble drug candidates. This method comprises incubation of preformed carrier systems with drug powder and subsequent determination of the resulting drug load of the carrier particles after removal of excess drug. For reliable routine use and to obtain meaningful loading results, information on the kinetics of the process is required. Passive loading proceeds via a dissolution-diffusion-based mechanism, where drug surface area and drug water solubility are key parameters for fast passive loading...
August 12, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28769774/fenofibrate-administration-reduces-alcohol-and-saccharin-intake-in-rats-possible-effects-at-peripheral-and-central-levels
#11
Mario Rivera-Meza, Daniel Muñoz, Erik Jerez, María E Quintanilla, Catalina Salinas-Luypaert, Katia Fernandez, Eduardo Karahanian
We have previously shown that the administration of fenofibrate to high-drinker UChB rats markedly reduces voluntary ethanol intake. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα) agonist, which induces the proliferation of peroxisomes in the liver, leading to increases in catalase levels that result in acetaldehyde accumulation at aversive levels in the blood when animals consume ethanol. In these new studies, we aimed to investigate if the effect of fenofibrate on ethanol intake is produced exclusively in the liver (increasing catalase and systemic levels of acetaldehyde) or there might be additional effects at central level...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28767589/effects-of-fenofibrate-on-inflammatory-cytokines-in-diabetic-retinopathy-patients
#12
Hai-Bing Ju, Fu-Xian Zhang, Shuang Wang, Jie Song, Tao Cui, Li-Feng Li, Hai-Yan Zhang
The role of cytokines in diabetic retinopathy (DR) and effects of fenofibrate on cytokines were explored by observing changes in serum IL-1β, TNF-α, VEGF, and Lp-PLA2 in different stages of DR and the intervention effect of oral fenofibrate on cytokines.In total, 190 patients with type 2 DR were enrolled and divided into 3 groups: diabetic without retinopathy (NDR) group (n = 30), nonproliferative diabetic retinopathy (NPDR) group (n = 80), and proliferative diabetic retinopathy (PDR) group (n = 80)...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28766701/rationale-for-an-adjunctive-therapy-with-fenofibrate-in-pharmacoresistant-nocturnal-frontal-lobe-epilepsy
#13
Monica Puligheddu, Miriam Melis, Giuliano Pillolla, Giulia Milioli, Liborio Parrino, Giovanni Mario Terzano, Sonia Aroni, Claudia Sagheddu, Francesco Marrosu, Marco Pistis, Anna Lisa Muntoni
OBJECTIVE: Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs are effective in about 55% of patients, whereas the rest remains refractory. One of the key pathogenetic mechanisms is a gain of function of neuronal nicotinic acetylcholine receptors (nAChRs) containing the mutated α4 or β2 subunits. Fenofibrate, a common lipid-regulating drug, is an agonist at peroxisome proliferator-activated receptor alpha (PPARα) that is a ligand-activated transcription factor, which negatively modulates the function of β2-containing nAChR...
August 2, 2017: Epilepsia
https://www.readbyqxmd.com/read/28752027/the-potential-of-natural-products-for-targeting-ppar%C3%AE
#14
REVIEW
Daniela Rigano, Carmina Sirignano, Orazio Taglialatela-Scafati
Peroxisome proliferator activated receptors (PPARs) α, -γ and -β/δ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil) and diabetes (thiazolidinediones, e...
July 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28749696/influence-of-physiological-gastrointestinal-surfactant-ratio-on-the-equilibrium-solubility-of-bcs-class-ii-drugs-investigated-using-a-four-component-mixture-design
#15
Zhou Zhou, Claire Dunn, Ibrahim Khadra, Clive G Wilson, Gavin W Halbert
The absorption of poorly water-soluble drugs is influenced by the luminal gastrointestinal fluid content and composition, which control solubility. Simulated intestinal fluids have been introduced into dissolution testing including endogenous amphiphiles and digested lipids at physiological levels; however, in vivo individual variation exists in the concentrations of these components, which will alter drug absorption through an effect on solubility. The use of a factorial design of experiment and varying media by introducing different levels of bile, lecithin, and digested lipids has been previously reported, but here we investigate the solubility variation of poorly soluble drugs through more complex biorelevant amphiphile interactions...
August 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28741179/activation-of-liver-x-receptor-inhibits-oct2-mediated-organic-cation-transport-in-renal-proximal-tubular-cells
#16
Teerasak Wongwan, Suticha Kittayaruksakul, Nithi Asavapanumas, Varanuj Chatsudthipong, Sunhapas Soodvilai
Liver X receptor (LXR) is transcriptional factor that plays an important role in the regulation of energy metabolism such as cholesterol, lipid, and glucose metabolism as well as membrane transporters and channels. Using both in vitro and in vivo models, LXR regulation of the expression and function of renal organic cation transporter 2 (OCT2) was observed. Synthetic LXR agonist (GW3965) and endogenous LXR agonist (22R-hydroxycholesterol) significantly reduced the uptake of (3)H-MPP(+), a prototypic substrate of OCT2, in both OCT2- Chinese hamster ovary K1 and human renal proximal tubular cells (RPTEC/TERT1)...
July 25, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28736931/genetic-variants-in-hsd17b3-smad3-and-ipo11-impact-circulating-lipids-in-response-to-fenofibrate-in-individuals-with-type-2-diabetes
#17
Daniel M Rotroff, Sonja S Pijut, Skylar W Marvel, John R Jack, Tammy M Havener, Aurora Pujol, Agatha Schluter, Greg A Graf, Henry N Ginsberg, Hetal S Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C Mychaleckyi, Howard L McLeod, John B Buse, Michael J Wagner, Alison A Motsinger-Reif
Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated T2D patients, we examined lipid changes in response to fenofibrate therapy using genome-wide association(GWA). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects(p<5x10(-6) )...
July 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28733879/anticancer-activity-of-salicin-and-fenofibrate
#18
Marwa Sabaa, Hassan M ELFayoumi, Shimaa Elshazly, Mahmoud Youns, Waleed Barakat
Cancer refers to a disorder of cell proliferation that leads to tumor production. Cancer is usually treated by surgery, chemotherapeutic drugs, and radiation. Despite the presence of many anticancer drugs, cancer is still an uncontrolled disease and is a major cause of death worldwide. In addition, most anticancer drugs have severe side effects that can limit their use in some patients. This study aims to investigate the possible anticancer activity of two clinically used drugs: a natural antioxidant agent (salicin) and an antihyperlipidemic agent (fenofibrate) against two breast cancer models (in vivo EAC and in vitro MCF7) and the pancreatic cancer cell line (Panc-1)...
July 21, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28733242/dual-centrifugation-a-new-technique-for-nanomilling-of-poorly-soluble-drugs-and-formulation-screening-by-an-doe-approach
#19
Martin Hagedorn, Ansgar Bögershausen, Matthias Rischer, Rolf Schubert, Ulrich Massing
The development of nanosuspensions of poorly soluble APIs takes a lot of time and high amount of active material is needed. In this publication the use of dual centrifugation (DC) for an effective and rapid API-nanomilling is described for the first time. DC differs from normal centrifugation by an additional rotation of the samples during centrifugation, resulting in a very fast and powerful movement of the samples inside the vials, which - in combination with milling beads - result in effective milling. DC-nanomilling was compared to conventional wet ball milling and results in same or even smaller particle sizes...
July 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28730672/lipid-lowering-therapy-of-everolimus-related-severe-hypertriglyceridaemia-in-a-pancreatic-neuroendocrine-tumour-pnet
#20
V De Gennaro Colonna, C Pavanello, F Rusconi, A Sartore-Bianchi, S Siena, S Castelnuovo, C R Sirtori, G Mombelli
WHAT IS KNOWN AND OBJECTIVE: Hypertriglyceridaemia (HTG) is a potentially serious side effect of everolimus therapy. We here report a case of severe HTG in an everolimus-treated patient and provide recommendations for its management. CASE SUMMARY: The patient was a 70-year-old woman, being treated with everolimus for a pancreatic neuroendocrine tumour (pNET). She developed severe HTG to a maximum of 969 mg/dL after 22 months of therapy. Treatment with fenofibrate rapidly normalized triglyceride (TG) levels...
July 21, 2017: Journal of Clinical Pharmacy and Therapeutics
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