Po-Ting Yeh1, Lu-Chun Wang2, Shu-Wen Chang3, Wei-Shiung Yang4,5, Chung-May Yang1,6, Chang-Hao Yang1,6. 1. Department of Ophthalmology, National Taiwan University Hospital , Taipei , Taiwan. 2. Department of Ophthalmology, National Taiwan University Hospital, Yun-Lin Branch , Douliou City, Yunlin County , Taiwan. 3. Department of Ophthalmology, Far Eastern Memorial Hospital , NewTaipei City , Taiwan. 4. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University , Taipei , Taiwan. 5. Department of Internal Medicine, National Taiwan University Hospital , Taipei , Taiwan. 6. Department of Ophthalmology, College of Medicine, National Taiwan University , Taipei , Taiwan.
Abstract
Purpose: To investigate the mechanisms of anti-inflammatory and anti-oxidative effects of fenofibrate, a peroxisome proliferator-activated receptors-α agonist, in preventing diabetic retinopathy (DR) progression via a diabetic rat model. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin in 6-week-old female Wistar rats. Diabetic rats were divided into diabetes without treatment (n = 10), diabetes treated with low dose fenofibrate (30 mg/kg/day) (n = 10) and high dose fenofibrate (100 mg/kg/day) (n = 10). Serum aqueous humor (AqH) and ocular tissues were gathered after 3-month treatment. Expressions of NF-κB and inflammatory chemokines (monocyte chemoattractant protein-1, fractalkine, and intercellular adhesion molecule-1) were detected by reverse transcription-polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and electrophoretic mobility shift assay. The levels of oxidative biomarkers, including acrolein, nitrotyrosine, and 8-hydroxy-2'-deoxyguanosin (8-OHdG), were determined by IHC and ELISA. The reactive oxygen species (ROS) levels in serum and AqH were measured by chemiluminescence methods. Results: After 3 months of treatment, the expressions of mRNA and protein of monocyte chemoattractant protein-1, fractalkine, and intercellular adhesion molecule-1 in the retina of diabetic rats were significantly inhibited by fenofibrate in a dose-dependent manner. These effects were mediated by inhibition of NF-κB by fenofibrate. The levels of oxidative markers, including acrolein, nitrotyrosine, and 8-OHdG, decreased in the retina of diabetic rats after fenofibrate treatment. The ROS levels in the AqH of diabetic rats also suppressed by fenofibrate. Conclusions: Fenofibrate significantly inhibited the expressions of NF-κB and inflammatory chemokines and reduced oxidative products within diabetic retina. Treatment of fenofibrate might be beneficial to preventing DR progression.
Purpose: To investigate the mechanisms of anti-inflammatory and anti-oxidative effects of fenofibrate, a peroxisome proliferator-activated receptors-α agonist, in preventing diabetic retinopathy (DR) progression via a diabeticrat model. Methods:Diabetes was induced by intraperitoneal injection of streptozotocin in 6-week-old female Wistar rats. Diabeticrats were divided into diabetes without treatment (n = 10), diabetes treated with low dose fenofibrate (30 mg/kg/day) (n = 10) and high dose fenofibrate (100 mg/kg/day) (n = 10). Serum aqueous humor (AqH) and ocular tissues were gathered after 3-month treatment. Expressions of NF-κB and inflammatory chemokines (monocyte chemoattractant protein-1, fractalkine, and intercellular adhesion molecule-1) were detected by reverse transcription-polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and electrophoretic mobility shift assay. The levels of oxidative biomarkers, including acrolein, nitrotyrosine, and 8-hydroxy-2'-deoxyguanosin (8-OHdG), were determined by IHC and ELISA. The reactive oxygen species (ROS) levels in serum and AqH were measured by chemiluminescence methods. Results: After 3 months of treatment, the expressions of mRNA and protein of monocyte chemoattractant protein-1, fractalkine, and intercellular adhesion molecule-1 in the retina of diabeticrats were significantly inhibited by fenofibrate in a dose-dependent manner. These effects were mediated by inhibition of NF-κB by fenofibrate. The levels of oxidative markers, including acrolein, nitrotyrosine, and 8-OHdG, decreased in the retina of diabeticrats after fenofibrate treatment. The ROS levels in the AqH of diabeticrats also suppressed by fenofibrate. Conclusions: Fenofibrate significantly inhibited the expressions of NF-κB and inflammatory chemokines and reduced oxidative products within diabetic retina. Treatment of fenofibrate might be beneficial to preventing DR progression.
Authors: María L Rodríguez; Salvador Pérez; Salvador Mena-Mollá; M Carmen Desco; Ángel Luis Ortega Journal: Oxid Med Cell Longev Date: 2019-11-11 Impact factor: 6.543
Authors: Samuel A Mills; Andrew I Jobling; Michael A Dixon; Bang V Bui; Kirstan A Vessey; Joanna A Phipps; Ursula Greferath; Gene Venables; Vickie H Y Wong; Connie H Y Wong; Zheng He; Flora Hui; James C Young; Josh Tonc; Elena Ivanova; Botir T Sagdullaev; Erica L Fletcher Journal: Proc Natl Acad Sci U S A Date: 2021-12-21 Impact factor: 11.205