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Sustained release of a novel non-fibrate PPARα agonist from microparticles for neuroprotection in murine models of age-related macular degeneration.
J Control Release
April 2025
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States of America. Electronic address:
Prior research has demonstrated the therapeutic potential of peroxisome proliferator-activated receptor α (PPARα) agonist fenofibrate on diabetic retinopathy. In the present study, a novel non-fibrate PPARα agonist, A190, was designed with higher potency and selectivity than fenofibrate in PPARα agonism. A190 was encapsulated in biodegradable microparticles (A190-MP) to ensure sustained drug release, with detection in the retina up to 6 months following a single intravitreal injection.
View Article and Find Full Text PDFNanocrystalline formulations typically contain stabilizing additives to minimize the risk of particle growth or agglomeration. This risk is particularly relevant when the nanosuspension is converted into a solid drug product as the original state of the nanosuspension should be restored upon redispersion of the drug product in vivo. In this work, the behavior of different nonionic and anionic surfactants in solid nanocrystalline formulations and their effects on redispersibility under biorelevant conditions were investigated.
View Article and Find Full Text PDFPeroxisome Proliferator-Activated Receptor Alpha Stimulation Preserves Renal Tight Junction Components in a Rat Model of Early-Stage Diabetic Nephropathy.
Int J Mol Sci
December 2024
Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Seccion XVI, Tlalpan, Mexico City 14080, Mexico.
Chronic hyperglycemia results in morphological and functional alterations of the kidney and microvascular damage, leading to diabetic nephropathy (DN). Since DN progresses to irreversible renal damage, it is important to elucidate a pharmacological strategy aimed for treating DN in the early stage. Here, we used the type 2 diabetic rat model to induce DN and show a nephroprotective effect following the stimulation of PPAR-α, which stabilized renal tight junction components claudin-2, claudin-5, and claudin-16.
View Article and Find Full Text PDFAmelioration of propionic acid-induced autism-like behaviors in rats by fenofibrate: A focus on reduction of brain galectin-3 levels.
Int J Dev Neurosci
December 2024
Department of Physiology, Demiroğlu Bilim University, Istanbul, Turkiye.
Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive behaviors. This study examines the effects of fenofibrate on a propionic acid (PPA)-induced rat model of ASD, focusing on behavioral changes, inflammatory markers, and histological findings.
Materials And Methods: Thirty male Wistar rats were divided into three groups: a control group, a group receiving PPA and saline, and a group treated with PPA and fenofibrate for 15 days.
Effect of fenofibrate on residual beta cell function in adults and adolescents with newly diagnosed type 1 diabetes: a randomised clinical trial.
Diabetologia
January 2025
Department of Clinical Research, Steno Diabetes Center Copenhagen, Copenhagen University Hospital, Herlev, Denmark.
Aims/hypothesis: Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, shows some promise in alleviating beta cell stress and preserving beta cell function in preclinical studies of type 1 diabetes. The aim of this phase 2, placebo-controlled, double-blinded, randomised clinical trial was to investigate the efficacy and safety of fenofibrate in adults and adolescents with newly diagnosed type 1 diabetes.
Methods: We enrolled 58 individuals (aged 16 to 40 years old) with newly diagnosed type 1 diabetes and randomised them to daily oral treatment with fenofibrate 160 mg or placebo for 52 weeks (in a block design with a block size of 4, assigned in a 1:1 ratio).
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