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

PLoS One. 2016 Jan 14;11(1):e0146438. doi: 10.1371/journal.pone.0146438. eCollection 2016.

Abstract

Purpose: We evaluated whether orally administered astaxanthin (AST) protects against oxidative damage in the ocular tissues of streptozotocin (STZ)-induced diabetic rats.

Methods and results: Fifty 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Aqueous Humor / metabolism
  • Blood Glucose
  • Body Weight
  • Chemokine CCL2 / metabolism
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Electroretinography
  • Female
  • Gene Expression
  • Gene Expression Regulation, Enzymologic / drug effects
  • Inflammation Mediators / metabolism*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lutein / pharmacology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects*
  • Protective Agents
  • RNA, Messenger / genetics
  • Rats
  • Retina / drug effects*
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Xanthophylls / pharmacology

Substances

  • Antioxidants
  • Blood Glucose
  • Chemokine CCL2
  • Inflammation Mediators
  • NF-kappa B
  • Protective Agents
  • RNA, Messenger
  • Xanthophylls
  • Intercellular Adhesion Molecule-1
  • astaxanthine
  • Lutein

Grants and funding

This study was supported by National Taiwan University Hospital Grants NTUH 101-001781. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.