L-Sulforaphane confers protection against oxidative stress in an in vitro model of age-related macular degeneration

Dulull, N, Dias, D, Thrimawithana, T and Kwa, F 2018, 'L-Sulforaphane confers protection against oxidative stress in an in vitro model of age-related macular degeneration', Current Molecular Pharmacology, vol. 11, no. 3, pp. 237-253.


Document type: Journal Article
Collection: Journal Articles

Title L-Sulforaphane confers protection against oxidative stress in an in vitro model of age-related macular degeneration
Author(s) Dulull, N
Dias, D
Thrimawithana, T
Kwa, F
Year 2018
Journal name Current Molecular Pharmacology
Volume number 11
Issue number 3
Start page 237
End page 253
Total pages 17
Publisher Bentham Science
Abstract BACKGROUND: In age-related macular degeneration, oxidative damage and abnormal neovascularization in the retina are caused by the upregulation of vascular endothelium growth factor and reduced expression of Glutathione-S-transferase genes. Current treatments are only palliative. Compounds from cruciferous vegetables (e.g. L-Sulforaphane) have been found to restore normal gene expression levels in diseases including cancer via the activity of histone deacetylases and DNA methyltransferases, thus retarding disease progression. OBJECTIVE: To examine L-Sulforaphane as a potential treatment to ameliorate aberrant levels of gene expression and metabolites observed in age-related macular degeneration. METHOD: The in vitro oxidative stress model of AMD was based on the exposure of Adult Retinal Pigment Epithelium-19 cell line to 200µM hydrogen peroxide. The effects of L-Sulforaphane on cell proliferation were determined by MTS assay. The role of GSTM1, VEGFA, DNMT1 and HDAC6 genes in modulating these effects were investigated using quantitative real-time polymerase chain reaction. The metabolic profiling of L-Sulforaphane-treated cells via gas-chromatography mass-spectrometry was established. Significant differences between control and treatment groups were validated using one-way ANOVA, student t test and post-hoc Bonferroni statistical tests (p<0.05). RESULTS: L-Sulforaphane induced a dose-dependent increase in cell cell proliferation in the presence of hydrogen peroxide by upregulating Glutathione-S-Transferase µ1 gene expression. Metabolic profiling revealed that L-Sulforaphane increased levels of 2-monopalmitoglycerol, 9, 12, 15,-(Z-Z-Z)-Octodecatrienoic acid, 2-[Bis(trimethylsilyl)amino]ethyl bis(trimethylsilyl)-phosphate and nonanoic acid but decreased β-alanine levels in the absence or presence of hydrogen peroxide, respectively. CONCLUSION: This study supports the use of L-Sulforaphane to promote regeneration of retinal cells under oxidative stress conditions.
Subject Vision Science
Keyword(s) Age-related macular degeneration
L-Sulforaphane
glutathione-S-transferase
metabolomic profiling
oxidative stress
retinal pigment epithelium
DOI - identifier 10.2174/1874467211666180125163009
Copyright notice © 2018 Bentham Science Publishers
ISSN 1874-4672
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