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Cited by 301

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

Flavonoids Protect Human Retinal Pigment Epithelial Cells from Oxidative-Stress–Induced Death

Hanneken, Anne, Lin, Fen-Fen, Johnson, Jennifer, Maher, Pamela·2006·Investigative Opthalmology & Visual Science
DOI 10.1167/iovs.04-1369
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Abstract

PURPOSE: To determine whether specific dietary and synthetic flavonoids can protect human retinal pigment epithelial (RPE) cells from oxidative-stress-induced death. METHODS: The efficacy and potency were determined of a variety of dietary and synthetic flavonoids on the survival of human ARPE-19 cells and primary human RPE cells treated with either hydrogen peroxide (H2O2) or t-butyl hydroperoxide (t-BOOH). We determined the effective concentrations (EC50s) and the toxicities (LD50s) of the flavonoids after 24 hours, by using the MTT assay. The efficacy of vitamins E and C on RPE cell survival were compared under identical conditions. The ability of specific flavonoids to protect RPE cells from cell death was determined at various time intervals after the cells were exposed to oxidative stress. The ability of flavonoids to block the accumulation of intracellular reactive oxygen species was examined with dichlorofluorescein (DCF) fluorescence. Finally, the ability of flavonoids to induce phase-2 detoxifying enzymes was tested by immunoblot analysis for the transcription factor Nrf2 and the phase-2 gene product heme-oxygenase 1. RESULTS: Specific flavonoids protected human RPE cells from oxidative-stress-induced death with efficacies between 80% and 100% and potencies in the high-nanomolar and low-micromolar range. The toxicities of most of the effective flavonoids were low. The effective flavonoids included the dietary flavonoids fisetin, luteolin, quercetin, eriodictyol, baicalein, galangin and EGCG, and the synthetic flavonoids, 3,6-dihydroxy flavonol and 3,7 dihydroxy flavonol. Several flavonoids can protect RPE cells even when they are added after the cells have been exposed to oxidative stress. The flavonoids acted through an intracellular route to block the accumulation of reactive oxygen species. Many of these flavonoids induced the expression of Nrf2 and the phase-2 gene product heme-oxygenase 1 in human RPE cells. CONCLUSIONS: The results identify a select group of flavonoids that protect RPE cells from oxidative-stress-induced death with a high degree of potency and low toxicity. Many of these flavonoids also induce the expression of phase-2 detoxification proteins which could function to provide additional protection against oxidative stress. This select group of flavonoids and the foods that contain high levels of these compounds may have some clinical benefit for patients with retinal diseases associated with oxidative stress.

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Metadata

Authors
Hanneken, A., Lin, F.-F., Johnson, J., & Maher, P.
Venue
Investigative Opthalmology & Visual Science
Publisher
Association for Research in Vision and Ophthalmology (ARVO)
Published
2006-07-01
Volume
47
Issue
7
Pages
3164
ISSN
  • 0146-0404 (ISSN-L)
  • 1552-5783
DOI
10.1167/iovs.04-1369
OpenAlex
W1977633303
Cited by
301
References
38
FWCI
11.77
Type
journal article
Language
en
Open access
closed

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