Cilostazol Attenuates Retinal Oxidative Stress and Inflammation in a Streptozotocin-Induced Diabetic Animal Model

ABSTRACT

Purpose: To investigate the anti-oxidative and anti-inflammatory effects of cilostazol in the ocular tissues of streptozotocin (STZ)-induced diabetic rats.

Materials and methods: Diabetes was induced in 6-week-old Wistar rats via peritoneal injections of STZ. The treatment group received cilostazol 18 mg/kg/day for 8 weeks (n = 10), and the diabetic group received phosphate buffer solution (n = 20). The expression of oxidative stress and inflammatory mediators in the ocular tissues was then assessed by reverse-transcription polymerase chain reactions, immunohistochemical (IHC) staining, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA).

Results: Reverse-transcription polymerase chain reactions, IHC staining, Western blot analysis, and ELISA showed that cilostazol inhibited mRNA and protein expressions of intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and fractalkine in the retina and aqueous humor (AqH). Consistent with these findings, cilostazol attenuated the activation of nuclear factor-κB (NF-κB) in the diabetic rats. The levels of oxidatively modified DNA (8-OHdG), nitrotyrosine and oxidative lipids (acrolein) were also diminished in the cilostazol-treated group. Chemiluminescence analysis showed that reactive oxygen species (ROS) levels in the AqH was significantly higher in the diabetic rats than in the non-diabetic rats. Treatment with cilostazol significantly reduced the ROS levels in the AqH compared to the diabetic rats.

Conclusions: Our results indicated that cilostazol reduced inflammatory reactions and oxidative stress in diabetic eyes. The anti-inflammatory effects of cilostazol may be indirectly via reducing oxidative stress, inhibiting NF-κB activity, and subsequently decreasing inflammatory mediators. Cilostazol may be beneficial to prevent the progression of diabetic retinopathy.

KEYWORDS:

• Cilostazol
• diabetic retinopathy
• inflammation
• oxidative stress
• reactive oxygen species

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This work was supported by the National Taiwan University Hospital and Far Eastern Memorial Hospital, Taipei, Taiwan [Grant 98-FTN18].