Iron-generated hydroxyl radicals kill retinal cells in vivo: Effect of ferulic acid

H. M. Chao, Y. H. Chen, J. H. Liu, S. M. Lee, F. L. Lee, Y. Y. Chang, P. H. Yeh, W. H.T. Pan, C. W. Chi, T. Y. Liu, W. Y. Lui, L. T. Ho, C. D. Kuo, D. E. Lin, C. C. Chan, D. M. Yang, A. M.Y. Lin, F. P. Chao

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Siderosis bulbi is vision threatening. An investigation into its mechanisms and management is crucial. Experimental siderosis was established by intravitreous administration of an iron particle (chronic) or FeSO4 (acute). After siderosis, there was a significant dose-responsive reduction in eletroretinogram (a/b-wave) amplitude, and an increase in OH level, greater when caused by 24 mM FeSO4 than that by 8 mM FeSO 4. Furthermore, the FeSO4-induced oxidative stress was significantly blunted by 100 μM ferulic acid (FA). Siderosis also resulted in an excessive glutamate release, increased [Ca++]i, and enhanced superoxide dismutase immunoreactivity. The latter finding was consistent with the Western blot result. Obvious disorganization including loss of photoreceptor outer segments and cholinergic amacrines together with a wide-spreading ferric distribution across the retina was present, which were related to the eletro-retinographic and pathologic dysfunctions. Furthermore, b-wave reduction and amacrine damage were respectively, significantly, dose-dependently, and clearly ameliorated by FA. Thus, siderosis stimulates oxidative stress, and possibly, subsequent excitotoxicity, and calcium influx, which explains why the retina is impaired electro-physiologically and pathologically. Importantly, FA protects iron toxicity perhaps by acting as a free radical scavenger. This provides an approach to the study and treatment of the iron-related disorders such as retained intraocular iron and Alzheimer disease.

Original languageEnglish
Pages (from-to)327-339
Number of pages13
JournalHuman and Experimental Toxicology
Volume27
Issue number4
DOIs
StatePublished - Apr 2008

Keywords

  • •OH
  • Ca++
  • Ferulic acid
  • Glutamate
  • Iron

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