Beneficial Effects of Fenofibric Acid on Overexpression of Extracellular Matrix Components, COX-2, and Impairment of Endothelial Permeability Associated with Diabetic Retinopathy.
Abstract
In the Fenofibric Acid (FA) Intervention and Event Lowering in Diabetes (FIELD) study, FA, a lipid-lowering drug, has been shown to significantly reduce macular edema in diabetic patients. In the present study, we investigated whether FA reduces vascular permeability by inhibiting cyclooxygenase-2 (COX-2), a critical mediator of inflammation, and reducing overexpression of fibronectin (FN) and collagen IV (Coll IV), two basement membrane (BM) components upregulated in diabetic retinopathy. Rat retinal endothelial cells (RRECs) were grown in normal (N:5 mM glucose) or high (HG:30 mM glucose) medium...
Source: Experimental Eye Research - August 18, 2015 Category: Opthalmology Authors: Roy S, Kim D, Hernández C, Simó R, Roy S Tags: Exp Eye Res Source Type: research
Development of Omega-3 Phospholipid-based Solid Dispersion of Fenofibrate for the Enhancement of Oral Bioavailability.
Abstract
This research aimed to develop the omega-3 phospholipids based solid dispersion to improve the oral bioavailability of fenofibrate. The omega-3 phospholipids based solid dispersion formulation (OPSD) was prepared by an antisolvent precipitation with immediate freeze-drying and the optimal composition of the formulation was determined as the ratios of sucrose to krill oil of 5:1 (w/w), krill oil to fenofibrate of 1.5:1 (w/w), and antisolvent to solvent of 6:4 (v/v). The developed OPSD formulation was characterized by using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and dif...
Source: European Journal of Pharmaceutical Sciences - July 9, 2015 Category: Drugs & Pharmacology Authors: Yang L, Shao Y, Han HK Tags: Eur J Pharm Sci Source Type: research
Novel fenofibric acid-loaded controlled release pellet bioequivalent to choline fenofibrate-loaded commercial product in beagle dogs
In conclusion, this fenofibric acid-loaded controlled release pellet would be a potential alternative to the choline fenofibrate-loaded commercial product. Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - June 8, 2015 Category: Drugs & Pharmacology Source Type: research
Transcriptome Analysis of K-877 (a Novel Selective PPARα Modulator (SPPARMα))-Regulated Genes in Primary Human Hepatocytes and the Mouse Liver.
CONCLUSION: These results indicate that changes in the gene expression induced by K-877 treatment are mainly mediated through PPARα activation. K-877 regulates the hepatic gene expression as a SPPARMα and thus may improve dyslipidemia as well as metabolic disorders, such as metabolic syndrome and type 2 diabetes, without untoward side effects.
PMID: 26040752 [PubMed - as supplied by publisher] (Source: Journal of Atherosclerosis and Thrombosis)
Source: Journal of Atherosclerosis and Thrombosis - June 5, 2015 Category: Cardiology Tags: J Atheroscler Thromb Source Type: research
Fenofibrate prevents the disruption of the outer blood retinal barrier through downregulation of NF-κB activity
Conclusions
Our findings suggest that the anti-inflammatory effects of FA through inhibition of NF-κB activity play a key role in the beneficial effect of fenofibrate for treating DME. (Source: Acta Diabetologica)
Source: Acta Diabetologica - May 5, 2015 Category: Endocrinology Source Type: research
Fenofibrate subcellular distribution as a rationale for the intracranial delivery through biodegradable carrier.
Authors: Grabacka M, Waligorski P, Zapata A, Blake DA, Wyczechowska D, Wilk A, Rutkowska M, Vashistha H, Ayyala R, Ponnusamy T, John VT, Culicchia F, Wisniewska-Becker A, Reiss K
Abstract
Fenofibrate, a well-known normolipidemic drug, has been shown to exert strong anticancer effects against tumors of neuroectodermal origin including glioblastoma. Although some pharmacokinetic studies were performed in the past, data are still needed about the detailed subcellular and tissue distribution of fenofibrate (FF) and its active metabolite, fenofibric acid (FA), especially in respect to the treatment of intracran...
Source: Journal of Physiology and Pharmacology - April 24, 2015 Category: Drugs & Pharmacology Tags: J Physiol Pharmacol Source Type: research
Effect of fenofibrate on retinal neurodegeneration in an experimental model of type 2 diabetes
Abstract
There is now consistent evidence from two major clinical trials (the Fenofibrate Intervention and Event Lowering in Diabetes and the Action to Control Cardiovascular Risk in Diabetes Eye) that fenofibrate arrests the progression of diabetic retinopathy in type 2 diabetic patients. However, the underlying mechanisms of this beneficial effect remain to be elucidated. The aim of the study was to evaluate the potential effect of fenofibric acid (FA), the active metabolite of fenofibrate, in preventing retinal neurodegeneration in an experimental mouse model of type 2 diabetes. For this purpose, we ...
Source: Acta Diabetologica - February 1, 2015 Category: Endocrinology Source Type: research
Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention.
In this study, female Sprauge Dawley rats were divided into standard chow diets (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD+FF) randomly. The rats of latter two groups were given HFD feeding for 5 months, then HFD+FF rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months. The pathological and tensional changes, protein expression of eNOS, and ER stress related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA) and FF on EDV of thoracic aorta from normal female SD rats were observed. Ultimately the expression of ER stress related genes were assessed in pr...
Source: Biochemical and Biophysical Research communications - January 12, 2015 Category: Biochemistry Authors: Lu Y, Cheng J, Chen L, Li C, Chen G, Gui L, Shen B, Zhang Q Tags: Biochem Biophys Res Commun Source Type: research
The Lidose Hard Capsule Formulation of Fenofibrate is Suprabioavailable Compared to the Nanoparticle Tablet Formulation Under High-fat Fed Conditions.
CONCLUSION: Under high-fat fed conditions the extent of fenofibrate absorption was 37% higher for the 200 mg Lidose hard capsule compared to the 145 mg nanoparticle tablet, which is exactly as expected based on a mg-to-mg weight basis. The results of the present study underline the importance of assessing bioequivalence of fenofibrate formulations under identical fed conditions, and preferentially after a high-fat meal as this condition represents the worst-case scenario. Furthermore, the results of this study demonstrate that the 145 mg nanoparticle tablet is not bioequivalent to the 200 mg Lidose hard capsule when admini...
Source: J Pharm Pharm Sci - January 1, 2015 Category: Drugs & Pharmacology Authors: Verbeeck RK, Niet SD, Lebrun S, Tremege M, Rennie TW, Coffiner M, Streel B, Cahay B Tags: J Pharm Pharm Sci Source Type: research
Peroxisome Proliferator-Activated Receptors α and γ are Linked with Alcohol Consumption in Mice and Withdrawal and Dependence in Humans.
CONCLUSIONS: We provide convergent evidence using both mouse and human data for specific PPARs in alcohol action. Reduced EtOH intake in mice and the genetic association between AD or withdrawal in humans highlight the potential for repurposing FDA-approved PPARα or PPARγ agonists for the treatment of AD.
PMID: 25516156 [PubMed - as supplied by publisher] (Source: Alcoholism, Clinical and Experimental Research)
Source: Alcoholism, Clinical and Experimental Research - December 16, 2014 Category: Addiction Authors: Blednov YA, Benavidez JM, Black M, Ferguson LB, Schoenhard GL, Goate AM, Edenberg HJ, Wetherill L, Hesselbrock V, Foroud T, Adron Harris R Tags: Alcohol Clin Exp Res Source Type: research
Peroxisome Proliferator‐Activated Receptors α and γ are Linked with Alcohol Consumption in Mice and Withdrawal and Dependence in Humans
ConclusionsWe provide convergent evidence using both mouse and human data for specific PPARs in alcohol action. Reduced EtOH intake in mice and the genetic association between AD or withdrawal in humans highlight the potential for repurposing FDA‐approved PPARα or PPARγ agonists for the treatment of AD. (Source: Alcoholism: Clinical and Experimental Research)
Source: Alcoholism: Clinical and Experimental Research - December 16, 2014 Category: Addiction Authors: Yuri A. Blednov, Jillian M. Benavidez, Mendy Black, Laura B. Ferguson, Grant L. Schoenhard, Alison M. Goate, Howard J. Edenberg, Leah Wetherill, Victor Hesselbrock, Tatiana Foroud, R. Adron Harris Tags: Original Article Source Type: research
Neuroprotective Potential of Peroxisome Proliferator Activated Receptor- α Agonist in Cognitive Impairment in Parkinson's Disease: Behavioral, Biochemical, and PBPK Profile.
In this study, we have investigated the effect of fenofibrate, a PPAR- α agonist in cognitive impairment model in PD. Bilateral intranigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (100 µg/1 µL/side) produced significant cognitive dysfunctions. Fenofibrate treatment at 10, 30, and 100 mg/kg for twenty-five days was found to be neuroprotective and improved cognitive impairment in MPTP-induced PD model as evident from behavioral, biochemical (MDA, GSH, TNF- α , and IL-6), immunohistochemistry (TH), and DNA fragmentation (TUNEL positive cells) studies. Further, physiologically based phar...
Source: PPAR Research - November 25, 2014 Category: Genetics & Stem Cells Tags: PPAR Res Source Type: research
Protective and Antioxidant Effects of PPAR{alpha} in the Ischemic Retina [Retina]
Conclusions.
Peroxisome proliferator-activated receptor-alpha has a potent antiapoptotic effect in the ischemic retina. This protective effect may be mediated in part through downregulation of HIF-1α/Nox 4 and consequently alleviation of oxidative stress. (Source: Investigative Ophthalmology)
Source: Investigative Ophthalmology - July 23, 2014 Category: Opthalmology Authors: Moran, E., Ding, L., Wang, Z., Cheng, R., Chen, Q., Moore, R., Takahashi, Y., Ma, J.-x. Tags: Retina Source Type: research
PPAR{alpha} Regulates Mobilization and Homing of Endothelial Progenitor Cells Through the HIF-1{alpha}/SDF-1 Pathway [Retina]
Conclusions.
Peroxisome proliferator-activated receptor alpha suppresses ischemia-induced EPC mobilization and homing through inhibition of the HIF-1α/SDF-1 pathway. This represents a novel molecular mechanism for PPARα's antiangiogenic effects. (Source: Investigative Ophthalmology)
Source: Investigative Ophthalmology - June 19, 2014 Category: Opthalmology Authors: Wang, Z., Moran, E., Ding, L., Cheng, R., Xu, X., Ma, J.-x. Tags: Retina Source Type: research
Comparison of Pharmacokinetics of Two Fenofibrate Tablet Formulations in Healthy Human Subjects.
CONCLUSIONS: Both fenofibrate tablet formulations demonstrated equivalent rates and extent of systemic absorption, and hence were considered bioequivalent.
PMID: 24844853 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - May 17, 2014 Category: Drugs & Pharmacology Authors: Chachad SS, Gole M, Malhotra G, Naidu R Tags: Clin Ther Source Type: research
