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Protective Effect of Fenofibrate on Oxidative Stress-Induced Apoptosis in Retinal-Choroidal Vascular Endothelial Cells: Implication for Diabetic Retinopathy Treatment.

Authors
  • Hsu, Ying-Jung1
  • Lin, Chao-Wen1, 2
  • Cho, Sheng-Li3
  • Yang, Wei-Shiung1, 3
  • Yang, Chung-May2
  • Yang, Chang-Hao2
  • 1 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, No. 1, Jen Ai Road Section 1, Taipei 100, Taiwan. , (Taiwan)
  • 2 Department of Ophthalmology, National Taiwan University Hospital, No. 7, Zhongshan South Road, Taipei 100, Taiwan. , (Taiwan)
  • 3 Department of Internal Medicine, National Taiwan University Hospital, No. 7, Zhongshan South Road, Taipei 100, Taiwan. , (Taiwan)
Type
Published Article
Journal
Antioxidants
Publisher
MDPI AG
Publication Date
Aug 05, 2020
Volume
9
Issue
8
Identifiers
DOI: 10.3390/antiox9080712
PMID: 32764528
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Diabetic retinopathy (DR) is an important microvascular complication of diabetes and one of the leading causes of blindness in developed countries. Two large clinical studies showed that fenofibrate, a peroxisome proliferator-activated receptor type α (PPAR-α) agonist, reduces DR progression. We evaluated the protective effects of fenofibrate on retinal/choroidal vascular endothelial cells under oxidative stress and investigated the underlying mechanisms using RF/6A cells as the model system and paraquat (PQ) to induce oxidative stress. Pretreatment with fenofibrate suppressed reactive oxygen species (ROS) production, decreased cellular apoptosis, diminished the changes in the mitochondrial membrane potential, increased the mRNA levels of peroxiredoxin (Prx), thioredoxins (Trxs), B-cell lymphoma 2 (Bcl-2), and Bcl-xl, and reduced the level of B-cell lymphoma 2-associated X protein (Bax) in PQ-stimulated RF/6A cells. Western blot analysis revealed that fenofibrate repressed apoptosis through cytosolic and mitochondrial apoptosis signal-regulated kinase-1 (Ask)-Trx-related signaling pathways, including c-Jun amino-terminal kinase (JNK) phosphorylation, cytochrome c release, caspase 3 activation, and poly (ADP-ribose) polymerase-1 (PARP-1) cleavage. These protective effects of fenofibrate on RF/6A cells may be attributable to its anti-oxidative ability. Our research suggests that fenofibrate could serve as an effective adjunct therapy for ocular oxidative stress-related disorders, such as DR.

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