Effect of Fenofibrate on the Expression of Inflammatory Mediators in a Diabetic Rat Model

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-2ʹ-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.

KEYWORDS:

• Diabetic retinopathy
• fenofibrate
• inflammation
• NF-κB
• oxidative stress
• reactive oxygen species

Acknowledgments

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Declaration of Interests

All authors did not have any competing interests for each author.

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by the National Taiwan University Hospital and Far Eastern Memorial Hospital, Taipei, Taiwan [grant number 97-FTN18]; the National Science Council, The Executive Yuan, ROC [grant number 100-2314-B-002-060-MY3].