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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

Cytotoxicity of HNE in ARPE-19 cells grown with or without serum measured with the MTT assay (a) and the LDH assay (b).Results are expressed relative to control values of untreated control cells grown in the same medium. Data is combined from three independent experiments with 3–6 replicate samples per group in each experiment, and are represented as scatterplots with median. ns denotes not statistically significant, ***denotes p < 0.001, Mann–Whitney U-test.
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f2: Cytotoxicity of HNE in ARPE-19 cells grown with or without serum measured with the MTT assay (a) and the LDH assay (b).Results are expressed relative to control values of untreated control cells grown in the same medium. Data is combined from three independent experiments with 3–6 replicate samples per group in each experiment, and are represented as scatterplots with median. ns denotes not statistically significant, ***denotes p < 0.001, Mann–Whitney U-test.

Mentions: We examined the differences in the reactions of serum-starved and normally cultured ARPE-19 cells (i.e. in 10% FBS) under increased oxidative stress by culturing both groups of cells in the presence of 30 μM HNE. Our results show that ARPE-19 cells were more susceptible to cell death if they had been serum-starved for an extended period of time (Fig. 2). In the MTT test, exposure of ARPE-19 cells grown in the serum-containing medium to HNE had their cellular viability reduced to 56.4%, whereas cell viability was decreased to only 0.1% in cells grown in the serum-free medium (P < 0.001). In the LDH assay, we observed a substantial release of LDH into the medium after treatment of cells with HNE in both serum-containing and serum-free medium. This indicates that cells cultured in the presence of 10% FBS and treated with HNE retain their metabolic activity better but still suffer from at least transient loss of cell membrane integrity.


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)

Cytotoxicity of HNE in ARPE-19 cells grown with or without serum measured with the MTT assay (a) and the LDH assay (b).Results are expressed relative to control values of untreated control cells grown in the same medium. Data is combined from three independent experiments with 3–6 replicate samples per group in each experiment, and are represented as scatterplots with median. ns denotes not statistically significant, ***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

f2: Cytotoxicity of HNE in ARPE-19 cells grown with or without serum measured with the MTT assay (a) and the LDH assay (b).Results are expressed relative to control values of untreated control cells grown in the same medium. Data is combined from three independent experiments with 3–6 replicate samples per group in each experiment, and are represented as scatterplots with median. ns denotes not statistically significant, ***denotes p < 0.001, Mann–Whitney U-test.
Mentions: We examined the differences in the reactions of serum-starved and normally cultured ARPE-19 cells (i.e. in 10% FBS) under increased oxidative stress by culturing both groups of cells in the presence of 30 μM HNE. Our results show that ARPE-19 cells were more susceptible to cell death if they had been serum-starved for an extended period of time (Fig. 2). In the MTT test, exposure of ARPE-19 cells grown in the serum-containing medium to HNE had their cellular viability reduced to 56.4%, whereas cell viability was decreased to only 0.1% in cells grown in the serum-free medium (P < 0.001). In the LDH assay, we observed a substantial release of LDH into the medium after treatment of cells with HNE in both serum-containing and serum-free medium. This indicates that cells cultured in the presence of 10% FBS and treated with HNE retain their metabolic activity better but still suffer from at least transient loss of cell membrane integrity.

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