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Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation.

Hytti M, Piippo N, Korhonen E, Honkakoski P, Kaarniranta K, Kauppinen A - Sci Rep (2015)

Bottom Line: Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation.The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1.The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.

ABSTRACT
Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

No MeSH data available.


Related in: MedlinePlus

Effect of fisetin and luteolin on the HNE-induced cytotoxicity in serum-starved ARPE cells.Cytotoxicity was determined with the MTT assay (a) and the LDH assay (b). Both fisetin and luteolin (at 50 μM) improved cell survival after an exposure to HNE and the solvent DMSO. Results are shown as scatterplots with median and are combined from 4–16 independent experiments with 3–4 parallel determinations per group/experiment. ***denotes p < 0.001, Mann–Whitney U-test.
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f3: Effect of fisetin and luteolin on the HNE-induced cytotoxicity in serum-starved ARPE cells.Cytotoxicity was determined with the MTT assay (a) and the LDH assay (b). Both fisetin and luteolin (at 50 μM) improved cell survival after an exposure to HNE and the solvent DMSO. Results are shown as scatterplots with median and are combined from 4–16 independent experiments with 3–4 parallel determinations per group/experiment. ***denotes p < 0.001, Mann–Whitney U-test.

Mentions: We next evaluated whether treatment with either 50 μM fisetin or luteolin could protect ARPE-19 cells from HNE-induced toxicity. Additionally, in order to assess the therapeutic potential of the polyphenols, both fisetin and luteolin were added 1 h after the initial exposure to HNE. Our data show that the polyphenols were able to rescue a significant fraction of serum-starved cells, as measured by the MTT assay (Fig. 3a, p < 0.0001 for both fisetin and luteolin). When compared to untreated controls, the average cell survival rate increased from 0.5% of HNE-treated cells to 30.4% and 35.7% in cells co-treated with fisetin or luteolin, respectively. Similarly to the results in the MTT assay, we found that the release of LDH was significantly lower in cells treated with fisetin or luteolin 1 h after HNE treatment (Fig. 3b, p < 0.0001 for both fisetin and luteolin).


Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation.

Hytti M, Piippo N, Korhonen E, Honkakoski P, Kaarniranta K, Kauppinen A - Sci Rep (2015)

Effect of fisetin and luteolin on the HNE-induced cytotoxicity in serum-starved ARPE cells.Cytotoxicity was determined with the MTT assay (a) and the LDH assay (b). Both fisetin and luteolin (at 50 μM) improved cell survival after an exposure to HNE and the solvent DMSO. Results are shown as scatterplots with median and are combined from 4–16 independent experiments with 3–4 parallel determinations per group/experiment. ***denotes p < 0.001, Mann–Whitney U-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664957&req=5

f3: Effect of fisetin and luteolin on the HNE-induced cytotoxicity in serum-starved ARPE cells.Cytotoxicity was determined with the MTT assay (a) and the LDH assay (b). Both fisetin and luteolin (at 50 μM) improved cell survival after an exposure to HNE and the solvent DMSO. Results are shown as scatterplots with median and are combined from 4–16 independent experiments with 3–4 parallel determinations per group/experiment. ***denotes p < 0.001, Mann–Whitney U-test.
Mentions: We next evaluated whether treatment with either 50 μM fisetin or luteolin could protect ARPE-19 cells from HNE-induced toxicity. Additionally, in order to assess the therapeutic potential of the polyphenols, both fisetin and luteolin were added 1 h after the initial exposure to HNE. Our data show that the polyphenols were able to rescue a significant fraction of serum-starved cells, as measured by the MTT assay (Fig. 3a, p < 0.0001 for both fisetin and luteolin). When compared to untreated controls, the average cell survival rate increased from 0.5% of HNE-treated cells to 30.4% and 35.7% in cells co-treated with fisetin or luteolin, respectively. Similarly to the results in the MTT assay, we found that the release of LDH was significantly lower in cells treated with fisetin or luteolin 1 h after HNE treatment (Fig. 3b, p < 0.0001 for both fisetin and luteolin).

Bottom Line: Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation.The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1.The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.

ABSTRACT
Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

No MeSH data available.


Related in: MedlinePlus