Astaxanthin Inhibits Expression of Retinal Oxidative Stress and Inflammatory Mediators in Streptozotocin-Induced Diabetic Rats

Po-Ting Yeh,Wei-Shiung Yang,Chang-Hao Yang,Chung-May Yang,Hsin-Wei Huang,Naren L Banik

doi:10.1371/journal.pone.0146438

Abstract

PurposeWe evaluated whether orally administered astaxanthin (AST) protects against oxidative damage in the ocular tissues of streptozotocin (STZ)-induced diabetic rats.Methods and ResultsFifty 6-week-old female Wistar rats were randomly assigned to receive an injection of STZ to induce diabetes (n = 40) or to remain uninduced (n = 10). The diabetic rats were randomly selected into four groups and they were separately administered normal saline, 0.6 mg/kg AST, 3 mg/kg AST, or 0.5 mg/kg lutein daily for eight weeks. Retinal functions of each group were evaluated by electroretinography. The expression of oxidative stress and inflammatory mediators in the ocular tissues was then assessed by immunohistochemistry, western blot analysis, ELISA, RT-PCR, and electrophoretic mobility shift assay (EMSA). Retinal functions were preserved by AST and lutein in different levels. Ocular tissues from AST- and lutein-treated rats had significantly reduced levels of oxidative stress mediators (8-hydroxy-2'-deoxyguanosine, nitrotyrosine, and acrolein) and inflammatory mediators (intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and fractalkine), increased levels of antioxidant enzymes (heme oxygenase-1 and peroxiredoxin), and reduced activity of the transcription factor nuclear factor-kappaB (NF-κB).ConclusionThe xanthophyll carotenoids AST and lutein have neuroprotective effects and reduce ocular oxidative stress, and inflammation in the STZ diabetic rat model, which may be mediated by downregulation of NF-κB activity.

Highlights

Diabetes are metabolic disorders characterized by dysregulation of blood glucose levels
The xanthophyll carotenoids AST and lutein have neuroprotective effects and reduce ocular oxidative stress, and inflammation in the STZ diabetic rat model, which may be mediated by downregulation of NF-κB activity
We examined the effects of AST on the production of oxidative stress mediators, the activation of NF-κB, and the expression of downstream inflammatory mediators in the ocular tissues of diabetic rats

Summary

Introduction

Diabetes are metabolic disorders characterized by dysregulation of blood glucose levels. Diabetic retinopathy is the most serious sight-threatening complication of diabetes [1, 2]. The hyperglycemia that occurs in diabetes increases the production of reactive oxygen species (ROS) and depletes cellular antioxidant defense capacities, resulting in enhanced oxidative stress. Chronic oxidative stress is considered one of the primary causes of diabetic retinopathy [3,4,5,6,7]. The retina has a high content of unsaturated fatty acids and high oxygen uptake, which increases lipid oxidation and ROS production. This is commonly thought to make the retina more vulnerable than any other tissue to oxidative stress damage [8, 9]

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Conclusion